Systems and methods for thrombolysis and delivery of an agent

ABSTRACT

A system for aspirating thrombus and delivering an agent including an aspiration catheter having an aspiration lumen and a supply lumen, and at least one orifice at or adjacent a distal end of the supply lumen and in fluid communication with the aspiration lumen, the at least one orifice located proximally of the open distal end of the aspiration lumen, wherein the at least one orifice is configured to create a spray pattern when pressurized fluid is pumped through the supply lumen such that the spray pattern is caused to impinge on a deflection element disposed opposite the at least one orifice when a distal end of the aspiration catheter is immersed within an aqueous environment, and such that the spray pattern upon impinging on the deflecting elements is caused to deflect, transforming into at least a substantially distally-oriented flow configured to exit the open distal end of the aspiration lumen.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/591,471, filed Oct. 2, 2019, which is a continuation of U.S. patentapplication Ser. No. 15/480,354, filed on Apr. 5, 2017, now U.S. Pat.No. 10,492,805, which claims the benefit of priority to U.S. ProvisionalApplication No. 62/318,972, filed on Apr. 6, 2016, all of which areincorporated by reference in their entireties herein for all purposes.Priority is claimed pursuant to 35 U.S.C. § 120 and 35 U.S.C. § 119.

BACKGROUND OF THE INVENTION Field of the Invention

The present disclosure pertains generally to medical devices and methodsof their use. More particularly, the present invention pertains toaspiration and thrombectomy devices and methods of use thereof.

Description of the Related Art

Several devices and systems already exist to aid in the removal ofthrombotic material. These include simple aspiration tube type devicesusing vacuum syringes to extract thrombus into the syringe, simpleflush-and-aspirate devices, more complex devices with rotatingcomponents that pull in, macerate and transport thrombotic material awayfrom the distal tip using a mechanical auger, systems that use very highpressure to macerate the thrombus and create a venturi effect to flushthe macerated material away.

All of the devices described above have limitations as a result ofindividual design characteristics. For example, simple aspirationcatheters offer ease of use and rapid deployment but may become blockedor otherwise inoperable when faced with older, more organized thromboticmaterial. Such devices must be removed and cleared outside the body andthen re-inserted into the vasculature, which lengthens the time neededfor the procedure and increases the opportunity to kink the cathetershaft. Such kinks may reduce performance by decreasing thecross-sectional area of the catheter or may render the deviceinoperable.

Mechanical rotary devices use an auger to grab and carry the thrombusaway from the target area. Some create transport force via vacuumbottles while others create differential pressure at the distal tip ofthe device with the auger acting as a low pressure pump. These devicestypically work slowly and offer the physician no feedback as to when thedevice should be advanced further into the lesion.

Flushing type devices include manual flush type devices in which thephysician manipulates a hand-driven pump to provide flowing saline atthe tip of the device to break up and aspirate the thrombus material,which may introduce performance variations based on the ability of thephysician to consistently pump the device over the duration of theprocedure. Flushing devices also include high pressure flushing devicesthat macerate the thrombus and then, using a vortex created by the highpressure fluid, transport the emulsified thrombotic material to acollection bag. These devices are effective at removing all levels ofthrombotic material, but the pressure created by the device is so greatthat its action against certain vessel walls may interrupt the heartmuscle stimulation mechanism and create a bradycardia event in certainpatients, sometimes requiring that a pacing lead be placed in thepatient prior to use. Further, interacting with the thrombotic materialoutside of the catheter may allow loose material to escape the capturemechanism.

BRIEF SUMMARY

In one embodiment of the present disclosure, a system for aspiratingthrombus and delivering an agent includes an aspiration catheter havinga supply lumen and an aspiration lumen, the supply lumen having aproximal end, a distal end, and a wall, the aspiration lumen having aproximal end, an open distal end, and an interior wall surface adjacentthe open distal end, and at least one orifice at or adjacent the distalend of the supply lumen, in fluid communication with the aspirationlumen, the at least one orifice located proximally of the open distalend of the aspiration lumen, wherein the at least one orifice isconfigured to create a spray pattern when pressurized fluid is pumpedthrough the supply lumen such that the spray pattern is caused toimpinge on the interior wall surface of the aspiration lumen when adistal end of the aspiration catheter is immersed within an aqueousenvironment, and such that the spray pattern upon impinging on theinterior wall surface is caused to transform into at least asubstantially distally-oriented flow capable of exiting the open distalend of the aspiration lumen.

In another embodiment of the present disclosure, a method for deliveringan agent includes providing an aspiration catheter having a proximal endand a distal end and including a supply lumen having a proximal end, adistal end, and a wall, an aspiration lumen having a proximal end, anopen distal end, and an interior wall surface adjacent the open distalend, and at least one orifice at or adjacent the distal end of thesupply lumen, in fluid communication with the aspiration lumen, the atleast one orifice located proximally of the open distal end of theaspiration lumen, wherein the at least one orifice is configured tocreate a spray pattern when pressurized fluid is pumped through thesupply lumen, inserting the distal end of the aspiration catheter into ablood vessel such that the open distal end of the aspiration lumen isadjacent a thrombus, and injecting an agent through the supply lumensuch that the spray pattern of the agent generally flows in a firstdirection out of the at least one orifice and against the interior wallsurface of the aspiration lumen, whereby after the spray pattern of theagent reaches the interior wall surface of the aspiration lumen themajority of the spray pattern of the agent flows in a second directiondistally out the open end of the aspiration lumen and adjacent thethrombus, wherein the second direction is different from the firstdirection.

In yet another embodiment of the present disclosure, a method forvisualizing a thrombectomy process includes providing an aspirationcatheter having a supply lumen and an aspiration lumen, the supply lumenhaving a distal end and a wall, the aspiration lumen having an opendistal end and an interior wall surface, an orifice adjacent the distalend of the supply lumen, in fluid communication with the interior of theaspiration lumen, the orifice located proximally of the open distal endof the aspiration lumen, inserting the distal end of the aspirationcatheter into a blood vessel such that the open distal end of theaspiration lumen is adjacent a thrombus, injecting fluid including aradiopaque contrast media through the supply lumen while visualizing aradiographic or fluoroscopic image, and identifying a boundary of thethrombus.

In still another embodiment of the present disclosure, a system foraspirating thrombus includes an aspiration catheter having a supplylumen and an aspiration lumen, the supply lumen having a distal end anda wall, the aspiration lumen having an open distal end and an interiorwall surface, an orifice adjacent the distal end of the supply lumen, influid communication with the interior of the aspiration lumen, theorifice located proximally of the open distal end of the aspirationlumen, wherein the orifice is configured to create a spray pattern whenpressurized fluid is pumped through the supply lumen, and a mandrelhaving a proximal end and a distal end, the distal end including a curvegreater than 90°, and including a concave portion configured to engage adistal end of the aspiration catheter, wherein the orifice istranslatable in a transverse direction to a longitudinal axis of theaspiration catheter by traction applied on the mandrel.

In yet another embodiment of the present disclosure, a system foraspirating thrombus includes an aspiration catheter having a supplylumen and an aspiration lumen, the supply lumen having a distal end anda wall, the aspiration lumen having an open distal end and an interiorwall surface, an orifice adjacent the distal end of the supply lumen, influid communication with the interior of the aspiration lumen, theorifice located proximally of the open distal end of the aspirationlumen, wherein the orifice is configured to create a spray pattern whenpressurized fluid is pumped through the supply lumen such that the spraypattern impinges on the interior wall surface of the aspiration lumenwhen a distal end of the aspiration catheter is immersed within anaqueous environment, and an elongate wire having a proximal end and adistal end, the distal end including an enlarged portion, wherein theelongate wire is configured to be rotatable such that the enlargedportion is capable of disrupting at least a portion of a thrombus.

In still another embodiment of the present disclosure, a system forremoving intracranial blood or thrombus includes a probe having a supplychannel and an aspiration channel, the aspiration channel having adistal end and a proximal end, the supply channel having a distal endand a wall, the aspiration channel having an opening at or adjacent itsdistal end and an interior wall surface, an orifice adjacent the distalend of the supply channel and in fluid communication with the interiorof the aspiration channel, wherein the orifice is configured to create aspray pattern when pressurized fluid is pumped through the supplychannel such that the spray pattern impinges on the interior wallsurface of the aspiration channel, and an ultrasound device at oradjacent the opening of the aspiration channel, and configured tooperate at a frequency of between about 1 kHz and about 20 MHz.

In yet another embodiment of the present disclosure, a method forremoving intracranial blood or thrombus from a patient includes placingan introducer through an aperture formed in the patient's skull, placinga trocar through the introducer, advancing an ultrasound device throughthe trocar to a treatment location within the intracranial space,transmitting ultrasound energy at one or more frequencies between about1 kHz and about 20 MHz from the ultrasound device, and removing theblood or thrombus from the patient through a probe having a supplychannel and an aspiration channel, the aspiration channel having adistal end and a proximal end, the supply channel having a distal endand a wall, the aspiration channel having an opening at or adjacent itsdistal end and an interior wall surface, an orifice adjacent the distalend of the supply channel and in fluid communication with the interiorof the aspiration channel, wherein the orifice is configured to create aspray pattern when pressurized fluid is pumped through the supplychannel such that the spray pattern impinges on the interior wallsurface of the aspiration channel, wherein the blood or thrombus isremoved through the aspiration channel.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of a system for aspirating thrombusaccording to an embodiment of the present disclosure.

FIG. 2 is a diagrammatic view showing more detail of the proximalportion of the system for aspirating thrombus of FIG. 1 .

FIG. 3 is a diagrammatic view of the distal end portion of the systemfor aspirating thrombus of FIG. 1 .

FIG. 4 is a plan view of disposable components of a system foraspirating thrombus according to an embodiment of the presentdisclosure.

FIG. 5 is a detailed view of detail 5 of FIG. 4 .

FIG. 6 is a detailed view of detail 6 of FIG. 4 .

FIG. 7 is a detailed view of detail 7 of FIG. 4 .

FIG. 8 is a detailed view of detail 8 of FIG. 4 .

FIG. 9 is a plan view of a distal end of an aspiration catheter of thesystem for aspirating thrombus of FIG. 4 .

FIG. 10 is a sectional view of FIG. 9 taken through line 10-10, asviewed within a blood vessel.

FIG. 11 is a detailed view of detail 11 of FIG. 10 .

FIG. 12 is elevation perspective view of a pump base according to anembodiment of the present disclosure.

FIG. 13 illustrates a piston of the system for aspirating thrombus beingcoupled to a saddle of a piston pump.

FIG. 14 is a cross-sectional view of the distal tip of the aspirationcatheter of FIG. 9 .

FIG. 15 is a view of a cassette for coupling to a pump base.

FIG. 16 is a sectional view of the cassette of FIG. 15 .

FIG. 17 is a partially exploded view of the pump base of FIG. 12 .

FIG. 18 is a graph of a pressure vs. time relationship of a piston pump.

FIG. 19 is an elevation view of a piston and a cassette of a piston pumpaccording to an embodiment of the present disclosure.

FIG. 20 is a graph of a pressure vs. time relationship of a piston pump.

FIG. 21 is a plan view of disposable components of a system foraspirating thrombus according to an embodiment of the presentdisclosure.

FIG. 22 is a detailed view of a catheter of the system for aspiratingthrombus of FIG. 21 .

FIG. 23 is a detailed view of a tubing set of the system for aspiratingthrombus of FIG. 21 .

FIG. 24 is an exploded view of a saline pump drive unit according to anembodiment of the present disclosure.

FIG. 25 is an exploded view of a disposable piston pump head of thesaline pump unit of FIG. 24 .

FIG. 26 is a sectional view of an aspiration catheter of a system foraspirating thrombus within a blood vessel according to an embodiment ofthe present disclosure.

FIG. 27 is a sectional view of a catheter within a blood vesseldelivering a drug to a target site.

FIG. 28 is a perspective view of an aspiration catheter according to anembodiment of the present disclosure.

FIG. 29 is a perspective view of an aspiration catheter according to anembodiment of the present disclosure.

FIG. 30 is a perspective view of an aspiration catheter according to anembodiment of the present disclosure.

FIG. 31 is a perspective view of an aspiration catheter according to anembodiment of the present disclosure.

FIG. 32 is a perspective view of the aspiration catheter of FIG. 28 witha significant negative pressure applied on the aspiration lumen.

FIG. 33 is a perspective view of the aspiration catheter of FIG. 29 witha significant negative pressure applied on the aspiration lumen.

FIG. 34 is a perspective view of the aspiration catheter of FIG. 30 witha significant negative pressure applied on the aspiration lumen.

FIG. 35 is a perspective view of the aspiration catheter of FIG. 31 witha significant negative pressure applied on the aspiration lumen.

FIG. 36 is a perspective view of the aspiration catheter of FIG. 28 withlittle or no negative pressure applied on the aspiration lumen.

FIG. 37 is a perspective view of the aspiration catheter of FIG. 29 withlittle or no negative pressure applied on the aspiration lumen.

FIG. 38 is a perspective view of the aspiration catheter of FIG. 30 withlittle or no negative pressure applied on the aspiration lumen.

FIG. 39 is a perspective view of the aspiration catheter of FIG. 31 withlittle or no negative pressure applied on the aspiration lumen.

FIG. 40 is a perspective view of the aspiration catheter of FIG. 28 witha particular negative pressure applied on the aspiration lumen.

FIG. 41 is a perspective view of the aspiration catheter of FIG. 30 witha particular negative pressure applied on the aspiration lumen.

FIG. 42 is a perspective view of an aspiration catheter according to anembodiment of the present disclosure.

FIG. 43 is a perspective view of an aspiration catheter according to anembodiment of the present disclosure.

FIG. 44A is an end view of an aspiration catheter according to anembodiment of the present disclosure.

FIG. 44B is a longitudinal sectional view of an aspiration catheteraccording to an embodiment of the present disclosure.

FIG. 45A is an end view of an aspiration catheter according to anembodiment of the present disclosure.

FIG. 45B is a longitudinal sectional view of an aspiration catheteraccording to an embodiment of the present disclosure.

FIG. 46A is a longitudinal sectional view of an aspiration catheter in afirst state according to an embodiment of the present disclosure.

FIG. 46B is a longitudinal sectional view of the aspiration catheter ofFIG. 46A in a second state according to an embodiment of the presentdisclosure.

FIG. 47 is a sectional view of a spray pattern of an aspiration catheteraccording to an embodiment of the present disclosure.

FIG. 48 is a sectional view of a spray pattern of an aspiration catheteraccording to an embodiment of the present disclosure.

FIG. 49 is a partial cutaway view of a spray pattern of an aspirationcatheter according to an embodiment of the present disclosure.

FIG. 50 is a partial cutaway view of a spray pattern of an aspirationcatheter according to an embodiment of the present disclosure.

FIG. 51 is a partial cutaway view of a spray pattern of an aspirationcatheter according to an embodiment of the present disclosure.

FIG. 52 is a sectional view of a spray pattern of an aspiration catheteraccording to an embodiment of the present disclosure.

FIGS. 53-55 are sectional views of a thrombus/clot being treated by anaspiration catheter according to an embodiment of the presentdisclosure.

FIG. 56 is a sectional view of an aspiration system including anaspiration catheter and a curved mandrel tool, according to anembodiment of the present disclosure.

FIG. 57 is a sectional view of the aspiration system of FIG. 56 in adeflected state.

FIG. 58 is an elevation view of an aspiration system according to anembodiment of the present disclosure.

FIG. 59A is a sectional view of an aspiration system including anaspiration catheter and a spinning wire, according to an embodiment ofthe present disclosure.

FIG. 59B is an elevation view of a rotating device for rotating thespinning wire of the embodiment of FIG. 59A.

FIG. 60 is a sectional view of a system for removing intracranialthrombus or intracranial hematoma through a window, aperture, or hole inthe cranium of a patient.

FIG. 61 is an elevation view of a system having multiple fluid sourcesaccording to an embodiment of the present disclosure.

FIG. 62 is an elevation view of an aspiration system according to anembodiment of the present disclosure.

FIG. 63 is a longitudinal sectional view of an aspiration catheteraccording to an embodiment of the present disclosure.

FIG. 64 is a longitudinal sectional view of an aspiration catheteraccording to an embodiment of the present disclosure.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

For the following defined terms, these definitions shall be applied,unless a different definition is given in the claims or elsewhere inthis specification.

All numeric values are herein assumed to be modified by the term“about,” whether or not explicitly indicated. The term “about” generallyrefers to a range of numbers that one of skill in the art would considerequivalent to the recited value (i.e., having the same function orresult). In many instances, the terms “about” may include numbers thatare rounded to the nearest significant figure.

The recitation of numerical ranges by endpoints includes all numberswithin that range (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and5).

As used in this specification and the appended claims, the singularforms “a”, “an”, and “the” include plural referents unless the contentclearly dictates otherwise. As used in this specification and theappended claims, the term “or” is generally employed in its senseincluding “and/or” unless the content clearly dictates otherwise.

The following detailed description should be read with reference to thedrawings in which similar elements in different drawings are numberedthe same. The drawings, which are not necessarily to scale, depictillustrative embodiments and are not intended to limit the scope of theinvention.

FIG. 1 is a diagrammatic figure depicting an assisted aspiration system10. The aspiration system 10 includes a remote hand piece 12 thatcontains a fluid pump 26 and an operator control interface 6. In onecontemplated embodiment, the system 10 is a single use disposable unit.The aspiration system 10 may also include extension tubing 14, whichcontains a fluid irrigation lumen 2 (or high pressure injection lumen)and an aspiration lumen 4, and which allows independent manipulation ofa catheter 16 without requiring repositioning of the hand piece 12during a procedure performed with the aspiration system 10. Extensiontubing 14 may also act as a pressure accumulator. High pressure fluidflows from the pump 26, which may comprise a displacement pump, pulseswith each stroke of the pump 26, creating a sinusoidal pressure map withdistinct variations between the peaks and valleys of each sine wave.Extension tubing 14 may be matched to the pump 26 to expand and contractin unison with each pump pulse to reduce the variation in pressurecaused by the pump pulses to produce a smooth or smoother fluid flow attip of catheter 16. Any tubing having suitable compliancecharacteristics may be used. The extension tubing 14 may be permanentlyattached to the pump 26 or it may be attached to the pump 26 by aconnector 44. The connector 44 is preferably configured to ensure thatthe extension tubing 14 cannot be attached to the pump 26 incorrectly.

An interface connector 18 joins the extension tubing 14 and the catheter16 together. In one contemplated embodiment, the interface connector 18may contain a filter assembly 8 between high pressure fluid injectionlumen 2 of the extension tubing 14 and a high pressure injection lumen36 of the catheter 16 (FIG. 3 ). The catheter 16 and the extensiontubing 14 may be permanently joined by the interface connector 18.Alternatively, the interface connector 18 may contain a standardizedconnection so that a selected catheter 16 may be attached to theextension tubing 14.

Attached to the hand piece 12 are a fluid source 20 and a vacuum source22. A standard hospital saline bag may be used as fluid source 20; suchbags are readily available to the physician and provide the necessaryvolume to perform the procedure. Vacuum bottles may provide the vacuumsource 22, or the vacuum source 22 may be provided by a syringe, avacuum pump or other suitable vacuum sources.

In one contemplated embodiment, the catheter 16 has a variable stiffnessranging from stiffer at the proximal end to more flexible at the distalend. The variation in the stiffness of the catheter 16 may be achievedwith a single tube with no radial bonds between two adjacent tubingpieces. For example, the shaft of the catheter 16 may be made from asingle length of metal tube that has a spiral cut down the length of thetube to provide shaft flexibility. Variable stiffness may be created byvarying the pitch of the spiral cut through different lengths of themetal tube. For example, the pitch of the spiral cut may be greater(where the turns of the spiral cut are closer together) at the distalend of the device to provide greater flexibility. Conversely, the pitchof the spiral cut at the proximal end may be lower (where the turns ofthe spiral cut are further apart) to provide increased stiffness. Insome embodiments, a single jacket may cover the length of the metal tubeto provide for a vacuum tight catheter shaft. Other features of catheter16 are described with reference to FIG. 3 , below.

FIG. 2 is a diagrammatic view showing more detail of the hand piece 12and the proximal portion of assisted catheter aspiration system 10. Thehand piece 12 includes a control box 24 where the power and controlsystems are disposed. The pump 26 may in some embodiments be a motordriven displacement pump that has a constant output. The pumpdisplacement relationship to the catheter volume, along with thelocation of the orifice 42 (exit) of the catheter high pressure lumen 36within the aspiration lumen 38 (FIG. 3 ), ensures that no energy istransferred to the patient from the saline pump as substantially allpressurized fluid is evacuated by the aspiration lumen. A prime button28 is mechanically connected to a prime valve 30. When preparing thedevice for use, it is advantageous to evacuate all air from thepressurized fluid system to reduce the possibility of air embolization.By depressing the prime button 28, the user connects the fluid source 20to the vacuum source 22 via the pump 26. This forcefully pulls fluid(for example 0.9% NaCl solution, or “saline”, or “normal saline”, orheparinized saline) through the entire pump system, removing all air andpositively priming the system for safe operation. A pressure/vacuumvalve 32 is used to turn the vacuum on and off synchronously with thefluid pressure system. One contemplated valve 32 is a ported one wayvalve. Such a valve is advantageous with respect to manual or electronicvalve systems because it acts as a tamper proof safety feature bymechanically and automatically combining the operations of the twoprimary systems. By having pressure/vacuum valve 32, the possibility ofturning the vacuum on without also activating the fluid system iseliminated.

The operator control interface 6 is powered by a power system 48 (suchas a battery or an electrical line), and may comprise an electroniccontrol board 50, which may be operated by a user by use of one or moreswitches 52 and one or more indicator lamps 54. The control board 50also monitors and controls several device safety functions, whichinclude over pressure detection, air bubble detection, and vacuumcharge. A pressure sensor 64 monitors pressure (i.e. injectionpressure), and senses the presence of air bubbles. Alternatively, or inconjunction, an optical device 66 may be used to sense air bubbles. Inone contemplated embodiment, the pump pressure is proportional to theelectric current needed to produce that pressure. Consequently, if theelectric current required by pump 26 exceeds a preset limit, the controlboard 50 will disable the pump 26 by cutting power to it. Air bubbledetection may also be monitored by monitoring the electrical currentrequired to drive the pump 26 at any particular moment. In order for adisplacement pump 26 to reach high fluid pressures, there should belittle or no air (which is highly compressible) present in the pump 26or connecting system (including the catheter 16 and the extension tubing14). The fluid volume is small enough that any air in the system willresult in no pressure being generated at the pump head. The controlboard monitors the pump current for any abrupt downward change that mayindicate that air has entered the system. If the rate of drop is fasterthan a preset limit, the control board 50 will disable the pump 26 bycutting power to it until the problem is corrected. Likewise, a block inthe high pressure lumen 36 (FIG. 3 ), which may be due to the entry oforganized or fibrous thrombus, or a solid embolus, may be detected bymonitoring the electrical current running the pump 26. In normal use,the current fluctuations of the pump 26 are relatively high. Forexample, the pump 26 may be configured so that there is a variation of200 milliAmps or greater in the current during normal operation, so thatwhen current fluctuations drop below 200 milliAmps, air is identified,and the system shuts down. Alternatively, current fluctuations in therange of, for example, 50 milliAmps to 75 milliAmps may be used toidentify that air is in the system. Additionally, an increase in thecurrent or current fluctuations may indicate the presence of clot orthrombus within the high pressure lumen 36. For example, a current ofgreater than 600 milliAmps may indicate that thrombus is partially orcompletely blocking the high pressure lumen 36, or even the aspirationlumen 38 (FIG. 3 ).

A vacuum line 56, connected to the vacuum source 22, may be connected toa pressure sensor 58. If the vacuum of the vacuum source 22 is low (i.e.the absolute value pressure has decreased) or if a leak is detected inthe vacuum line 56, the control board 50 disables the pump 26 until theproblem is corrected. The pressure sensor 58 may also be part of asafety circuit 60 that will not allow the pump 26 to run if a vacuum isnot present. Thereby, a comprehensive safety system 62, including thesafety circuit 60, the pressure sensor 64 and/or the optical device 66,and the pressure sensor 58, requires both pump pressure and vacuumpressure for the system to run. If a problem exists (for example, ifthere is either an unacceptably low pump pressure or an absence ofsignificant vacuum), the control board 50 will not allow the user tooperate the aspiration system 10 until all problems are corrected. Thiswill keep air from being injected into a patient, and will assure thatthe aspiration system 10 is not operated at incorrect parameters.Alternatively, in lieu of a direct connection (e.g., electrical,optical), the pressure sensor 58 can be configured to send a wirelesssignal to the control board 50, or any other component (e.g., antenna)coupled to or in communication with the control board 50, to remotelycontrol operation of the pump 26. The remote control may be possible,whether the pump is within the sterile field or outside the sterilefield.

FIG. 3 is a diagrammatic view of the distal end portion 68 of theassisted catheter aspiration system 10, showing more details of thecatheter 16. The catheter 16 in some embodiments is a single-operatorexchange catheter and includes a short guidewire lumen 34 attached tothe distal end of the device. The guidewire lumen 34 can be betweenabout 1 and about 30 cm in length, or between about 5 and about 25 cm inlength, or between about 5 and about 20 cm in length, or approximately13.5 cm in length. In other embodiments, a full-length guidewire lumen(extending the length of the catheter 16) may be used. For example, acatheter 16 sized to be used on peripheral blood vessels, includingperipheral arteries, may incorporate a full-length guidewire lumen. Insome embodiments, the aspiration itself may also serve as a guidewirelumen. An aspiration lumen 38 includes a distal opening 40 which allowsa vacuum (for example, from vacuum source 22) to draw thromboticmaterial into the aspiration lumen 38. A high pressure lumen 36 includesa distal orifice 42 that is set proximally of distal opening 40 by a setamount. For example, distal orifice 42 can be set proximally of distalopening 40 by about 0.508 mm (0.020 inches), or by 0.508 mm±0.076 mm(0.020 inches±0.003 inches) or by another desired amount. The orifice 42is configured to spray across the aspiration lumen to macerate and/ordilute the thrombotic material for transport to vacuum source 22, forexample, by lowering the effective viscosity of the thrombotic material.The axial placement of the fluid orifice 42 is such that the spraypattern interaction with the opposing lumen wall preferably produces aspray mist and not a swirl pattern that could force embolic material outfrom the distal opening 40. The spray pattern may be present at leastwhen a distal end of the catheter 16 is within an aqueous environment,such as a body lumen, including a blood vessel. The aqueous environmentmay be at body temperature, for example between about 35.0° C. and about40.0° C., or between about 36.0° C. and about 38.0° C. The system may beconfigured so that the irrigation fluid leaves the pump at a pressure ofbetween about 3.447 megapascal (500 pounds per square inch) and about10.342 megapascal (1500 pounds per square inch). In some embodiments,after a pressure head loss along the high pressure lumen 36, theirrigation fluid leaves orifice 42 at between about 4.137 megapascal(600 pounds per square inch) and about 8.274 megapascal (1200 pounds persquare inch), or between about 4.816 megapascal (650 pounds per squareinch) and about 5.861 megapascal (850 pounds per square inch).

FIG. 4 illustrates a system for aspirating thrombus 100 according to anembodiment of the present invention. The system for aspirating thrombus100 depicted in FIG. 4 represents disposable components 101, comprisinga tubing set 103 and an aspiration catheter 118, which are configured toattach to a vacuum source 22, a fluid source 20 (FIGS. 1 and 2 ), apressure monitor (not shown), and a pump base 200 (FIG. 12 ). The systemfor aspirating thrombus 100 is also configured to be used with aguidewire. Beginning with the components of the tubing set 103, a spike102 (shown in more detail in FIG. 5 ) is configured to couple to a fluidsource 20 such as a saline bag. The saline bag may have a volume ofsaline equal to about 1000 ml or about 500 ml. The saline may comprisenormal saline, and may be heparinized, or may contain one or moretherapeutic agents. Other fluids may be used in place of normal salineor a saline mixture, including lactated Ringer's solution, hypertonicsaline, or even solutions containing blood products. The saline, orother fluid, may be at room temperature, or may be warmed or cooled(e.g., to permanently or temporarily increase or decrease activity). Aconnector 104 (shown in more detail in FIG. 7 ), for example a luerconnector, is configured to couple to a vacuum source 22. The vacuumsource 22 may be a vacuum bottle having a volume of between 20 ml and500 ml. The vacuum source 22 may instead be a 60 ml syringe whoseplunger is pulled back after coupling to the connector 104. This may bea lockable plunger, which is locked in order to maintain the evacuatedplunger position. In some cases, the vacuum source 22 may be a 20 mlsyringe or a 30 ml syringe. An exemplary syringe with a lockable plungeris the VacLok® syringe sold by Merit Medical Systems, Inc. of SouthJordan, Utah, USA. The vacuum source 22 may also be a vacuum pump, withor without a collection container. A pressure transducer 106 capable ofmeasuring vacuum (including positive pressure sensors that areconfigured to measure positive pressure, but are capable of measuringnegative pressure) is coupled to a vacuum line 108 via a y-connector110. Signals from the pressure transducer 106 travel along a cable 112(FIG. 7 ), which also supplies voltage to the pressure transducer 106. Aconnector 114 (also shown in FIG. 6 ) couples the cable 112 to apressure monitor or to the pump base 200. A cassette 116 is a disposablecomponent attachable to the pump base 200 (FIG. 12 ) for allowingpressurized injection of a liquid injectate (such as saline). Thecassette 116 is described in more detail in relation to FIG. 6 . Theaspiration catheter 118 having a distal end 120 is shown in more detailin FIG. 8 .

Turning to FIG. 5 , the spike 102 communicates with extension tubing122. Liquid injectate is pumped downstream at the piston pump, whichpulls more liquid injectate (for example from a saline bag) through acheck valve 126 and through a supply tube 130. An injection port 128 maybe used for injecting other materials into the system, or for removingair or priming the system. The spike 102 may be packaged with aremovable protective spike cover 124.

The cassette 116, as seen in FIG. 6 , pulls liquid injectate from thesupply tube 130, and pressurizes (in conjunction with the pump base 200)an injection tube 152. More detail of the cassette 116 will be describedalong with the description of the entire piston pump. FIG. 7 shows moredetail of the pressure transducer 106 for measuring the vacuum. Thepressure transducer 106 connects to the y-connector 110 with a luerfitting 154. The injection tube 152 and the vacuum line 108 communicateto lumens of a catheter shaft 142. For example, the injection tube 152may be fluidly connected to a distal supply tube 168 (FIGS. 9-11 ), forexample a polyimide or stainless steel or nitinol tube having highstrength thin walls. This distal supply tube 168 may reside within thecatheter shaft 142, with the annulus between forming an aspiration lumen160 (FIGS. 9-11 ). A strain relief 156 protects the catheter shaft 142from kinking and other damage. In any cases in which luer fittings 154are used (at any of the connections), a custom luer with an added o-ringmay be used in order to allow the connection to withstand elevatedpressures. In some embodiments, a bespoke connector may be utilized, toincrease high pressure endurance. In some embodiments, pressures as highas 6.89 megapascal (1,200 pounds per square inch) or greater may beachieved without leakage or without causing decoupling of the catheter.

Turning to FIG. 8 , the aspiration catheter 118 is illustrated as asingle-operator exchange catheter and includes a guidewire tube 132attached to the distal end 120 on one side of the aspiration catheter118. The guidewire tube 132 can be between about 1 and about 30 cm inlength, or between about 5 and about 25 cm in length, or between about 5and about 20 cm in length, or approximately 13.5 cm in length. Theguidewire tube 132 has a distal end 136 and a proximal end 138, and asingle guidewire lumen 134 passing between the two ends 136, 138. Theguidewire lumen 134 may be configured to be compatible with a 0.014″guidewire, a 0.018″ guidewire, or a number of other guidewire diameters.A lumen inner diameter may be about 0.406 mm (0.016 inches) forcompatibility with a 0.014″ guidewire. The guidewire tube 132 may beconstructed of a number of materials, including nylon, polyethylene,PEBAX®, polyester, PET, or may be constructed from composite orcoextruded materials. For example an inner layer may comprise highdensity polyethylene or FEP, PTFE, ETFE, or other materials for highlubricity, and an outer layer may include PEBAX, nylon or othermaterials, for combination mechanical strength and flexibility. A tielayer may be used between the inner and outer layers, for example linearlow density polyethylene. The catheter 118 may include a compositecatheter shaft 142 having an inner support structure 144 covered with apolymer jacket 146. The inner support structure 144 may be a tubularbraid or one or more helical coils, for example, made with stainlesssteel flat or round wires. The inner support structure 144 may also bespiral cut hypodermic tubing, for example made from 304 stainless steelor nickel-titanium. The spiral cut hypodermic tubing may have a pitchmeasuring about 4 to 6 millimeters, or about 5 millimeters at theproximal end for increased stiffness, transitioning to a pitch of about0.75 to 1 mm or about 0.87 mm, at the distal end 150 of the innersupport structure 144. In between these two different pitch sections,may be intermediate pitch sections, for example, a section having apitch of between about 2 mm and about 5 mm, and another section having apitch of about 1 mm to about 2.5 mm. The inner support structure 144 mayend at a transition zone 148, so that the polymer jacket 146 aloneextends to the distal end 136 of the aspiration catheter 118. A cathetertip portion 140 is described in more detail in relation to FIGS. 9-11 .

FIGS. 9-11 show an open distal end 158 of an aspiration lumen 160 foraspirating thrombus. A skive 162 may be formed in the polymer jacket146, to aid entry of thrombus 164 that is aspirated into the aspirationlumen 160 (in the direction of arrow 180) by the combination of thevacuum created by the vacuum source 22. The skive 162 also minimizes thechances of the open distal end 158 being sucked against a blood vesselwall 166. A distal supply tube 168 has a closed distal end 170, forexample, it may be occluded during manufacture using adhesive, epoxy,hot melt adhesive or an interference member. Alternatively, the distalsupply tube 168 may be closed off by melting a portion of it. The distalsupply tube 168 has a lumen 176 extending its length and an orifice 172formed through its wall 174 at a location adjacent and proximal to theclosed distal end 170. The orifice 172 may have a diameter between about0.0508 mm (0.002 inches) and about 0.1016 mm (0.004 inches), or about0.0787 mm (0.0031 inches). The inner diameter of the distal supply tube168 may be between about 0.3048 mm (0.012 inches) and about 0.4826 mm(0.019 inches), or between about 0.3556 mm (0.014 inches and about0.4318 mm (0.017 inches) or about 0.3937 mm (0.0155 inches). The lumen176 of the distal supply tube 168 is a continuation of an overall flowpath emanating from the fluid source 20 including the extension tubing122, the supply tube 130, the interior of the cassette 116, and theinjection tube 152. In some embodiments, the lumen 176 of the distalsupply tube 168 may taper, for example, from an inner diameter of about0.3937 mm (0.0155 inches) at a proximal portion to an inner diameter ofabout 0.2974 mm (0.011 inches) at a distal portion. In some embodiments,the equivalent of a taper may be achieved by bonding different diametertubing to each other, resulting in a stepped-down tubing inner diameter.In some embodiments, different diameter tapered tubing may be bonded toeach other, for a combination of tapering and step-down of diameter. Asdescribed in conjunction with the piston pump, a pump output pressurewave of about 4.137 megapascal (600 pounds per square inch) to about5.516 megapascal (800 pounds per square inch) causes a liquid injectateto flow through the flow path, including a distal supply tube 168(arrows 182), and causes a fluid jet 178 to exit the orifice 172 at ahigh velocity. The fluid jet 178, in absence of flow through theaspiration lumen 160 (for example if there is no vacuum), would impingeupon an inner wall 181 of the aspiration lumen 160 directly adjacent theorifice 172. Depending on the amount of vacuum present, the fluid jet,may curve as shown. The fluid jet 178 serves to macerate thrombus 164that enters the aspiration lumen 160, and dilutes it. The flow rate ofthe liquid injectate (e.g. saline) and the amount of vacuum arecontrolled so that about 50% to about 70% of the volume of the mixtureof the saline and blood flowing through the proximal aspiration lumen160 is blood. Or about 60% of the volume is blood. This maceration anddilution assures that there is continuous flow through the aspirationlumen 160 so that it will not clog. The fluid jet 178 is configured tobe contained within the aspiration lumen 160, and to not exit into ablood vessel or other body lumen.

The axial center of the orifice 172 is about 0.3302 mm (0.013 inches) toabout 0.8382 mm (0.033 inches), or about 0.4064 mm (0.016 inches) toabout 0.6604 mm (0.026 inches) proximal to the most proximal portion ofthe open distal end 158, as illustrated by distance D in FIG. 11 . FIG.14 is a cross-section of the catheter tip portion 140 at the axialcenter of the orifice 172. The orifice 172 is oriented approximatelyalong a vertical midline 184 of the aspiration lumen 160, or within arange of ±a, there where angle a is about 20°. The angle a, may bevaried in different embodiments between about 1° and about 45°, orbetween about 20° and about 35°. The guidewire tube 132 may be securedto the polymer jacket 146 with attachment materials 186, such asadhesive, epoxy, hot melt or other materials. The guidewire tube 132 maybe secured along its entire length, or at discrete locations along itslength, in order to maximize flexibility. The distal supply tube 168 maybe secured within the aspiration lumen 160 with attachment materials188, such as adhesive, epoxy, hot melt or other materials. The polymerjacket 146 may comprise a number of different materials, includingPEBAX, nylon, or polyurethane. In some embodiments, the polymer jacketmay be partially melt bonded to the distal supply tube 162 and/or theguidewire tube 132, in order to minimize the wall thickness of theassembly.

FIG. 12 illustrates a pump base 200 for coupling the cassette 116 of thesystem for aspiration of thrombus 100. A housing 202 is attached to anIV pole clamp 204, and contains the control circuitry and the motor foroperating a piston pump system 300 (FIG. 13 ) which comprises thecombined pump base 200 and the cassette 116. By action of a motor andcam within the pump base 200, a saddle 206 is cyclically actuated (upand down) within a window 208 to move a piston 210 within the cassette116 (FIG. 13 ). Pegs 212 of the cassette 116 insert into cavities 216 inthe pump base 200. Biased snaps 214 lock into one or more grooves 218 inthe pump base 200. Either the cavities 216 or the grooves 218, may haveone or more switches which sense the presence of the cassette 116. Forexample, the cassette for one particular model may have a first number(or combination) of pegs 212 or biased snaps 214, which anotherparticular model may have a different number (or combination) of pegs212 or biased snaps 214, which is recognized by the system. A smoothsurface 224 of an elastomeric frame 222 engages edges 220 of thecassette 116, for enhanced protection. An upper space 226 is configuredto engage, or closely match the supply tube 130 and a lower space 228 isconfigured to engage, or closely match the injection tube 152. Thesaddle 206 has a semi-cylindrical cavity 236 which snaps over acylindrical engagement surface 238 on the piston 210. The saddle alsohas an upper edge 240 and a lower edge 242 for axially engaging a firstabutment 244 and a second abutment 246, respectively, of the piston 210.A user interface 230 on the pump base 200 has one or more buttons 232and one or more indicators 234, which allow the user to operate andassess the operation of the system 100. For example, the buttons mayinclude a start button to begin pumping, a stop button to stop pumping,a prime button to prime the system with a fluid injectate and purge outair, or a temporary pause button. Other data entry keys are alsopossible. The cassette 116 may include one or more interface components248. For example, a resistor, whose value the pump base 200 is able tomeasure via contacts 247, 249 when the cassette 116 is attached to thepump base 200. This allows the pump base 200 to determine theappropriate parameter for operating a specific model of the system 100.For example, a first resistor having a first resistance may be used witha first model and a second resistor having a second resistance may beused with another model. Alternatively, the interface component 248 mayincorporate an RFID chip, such as a read RFID chip or a read/write RFIDchip. This may allow specific data (pump operating pressures, RPM ofmotor output, etc.) to be recorded within the pump base 200 or toconnected hardware and identified for each patient.

FIGS. 15 and 16 illustrate the cassette 116 with most of its internalcomponents visible. FIG. 16 is a sectional view of the cassette 116. Thecassette 116 comprises an internal supply cylinder 252 and an internalinjection cylinder 254, which are cylindrical cavities extending withinthe cassette 116. The piston 210 includes a supply side shaft 256 and aninjection side shaft 258, the supply side shaft 256 including an o-ring266 for sealably interfacing with the supply cylinder 252 and theinjection side shaft 258 including an o-ring 268 for sealablyinterfacing with the injection cylinder 254. Each of the o-rings 266,268 are within a cylindrical groove 290, 292 around each respectiveshaft portion 256, 258. An internal ball valve 272 (FIG. 16 ) stopsinjectate (saline) from flowing through an internal channel 274 in thesupply side shaft 256 of the piston 210 when the piston 210 moves in afirst direction 276, but the internal ball valve 272 allows injectate toflow through the internal channel 274 and through an internal channel282 in the injection side shaft 258 when the piston 210 moves in asecond direction 278. The ball valve 272 is axially held between aspherical annular recess 284 in the interior of the supply side shaft256 and a recess having thru channels 286 in the injection side shaft258. The supply side shaft 256 and the injection side shaft 258 may beheld together with a threaded connection 288. When the piston 210 movesin the first direction 276, the injection side shaft 258 of the piston210 and o-ring 268 force injectate through the injection tube 152. Aprotective tube 280 is shown over the injection tube 152. In FIG. 15 ,the injection side shaft 258 is shown at the bottom of an injectionpulse. Injectate is filtered through an in-line filter 262, which may bea 40 to 50 micron filter, having an approximate thickness of 0.762 mm(0.030 inches). The in-line filter 262 is configured to keep particulateout of the injectate. Even though injectate is circulated through theaspiration catheter 118, and not into the blood vessel, the filteringprovided by the in-line filter 262 is an extra safety step. However,this step helps assure that particulate does not block the small orifice172 (FIG. 11 ). When the piston 210 moves in the second direction 278,the supply side shaft 256 of the piston 210 and the o-ring 266 sealablymove together within the supply cylinder 252, but the ball valve 272allows the injectate to pass through the internal channels 274, 282 ofthe piston 210 and fill the injection cylinder 254. The injectate isable to enter from the supply tube 130 through a check valve assembly270 comprising an o-ring 264 and a check valve 250. The check valve 250allows injectate to enter the interior of the cassette 116 from thesupply tube 130, but not to move from the cassette 116 to the supplytube 130. The check valve 250 may be configured so that air, due atleast in part to its low viscosity, will not be able to cause the checkvalve 250 to move (open), thus not allowing air to progress through thesystem. In some embodiments, the piston 210 may be a single piece(monolithic) design with a bore into which a check-valve is press-fit orbonded. A check valve compatible with this assembly may be supplied bythe Lee Company of Westbrook, Conn., USA.

The volume of injectate injected per cycle may range from about 0.02 mlto about 41 ml, or from about 0.04 ml to about 2.0 ml, or about 0.06 mlto about 0.08 ml, or about 0.07 ml. The usable volume (volume that canbe injected) of the injection cylinder 254 may be configured to be lessthan the usable volume (volume that can be filled from) of the supplycylinder 252, in order to assure sufficient filling of the injectioncylinder 254. For example, the usable volume of the injection cylinder254 may be about 0.05 ml to about 0.12 ml, and the usable volume of thesupply cylinder 252 may be about 0.07 ml to about 0.16 ml. A usablevolume ratio Ru of between about 1.15 and about 2.00, or between about1.25 and about 1.85, or about 1.40 is contemplated, where:

-   -   R_(U)=V_(SCU)/V_(ICU), wherein:    -   V_(SCU)=Usable volume of the supply cylinder 252, and    -   V_(ICU)=Usable volume of the injection cylinder 254.

A mean flow rate of between about 5 ml/minute and about 100 ml/minute.In some embodiments for use in coronary applications, 20 ml/minute maybe desired. In some embodiments for use in peripheral applications, 50ml/minute may be desired.

FIG. 18 illustrates a graph 600 of a pressure (P) vs. time (T) curve 602of a piston pump. Peaks 604 and valley 606 of the curve 602 can bedependent upon the design of the piston and cylinders of the pistonpump, particularly of the usable volume ratio R_(U). Turning to FIG. 19, a piston 608 is illustrated having a first diameter D₁ and a seconddiameter D₂ measured at the compressed o-rings 601, 603 (when placedwithin cylinders 605 and 607 of a cassette 609). The diameters of thecylinders 605, 607 are thus also defined as diameters D₁ and D₂. Whenthe diameters D₁, D₂, and the lengths of the cylinders 605, 607 areadjusted such that the usable volume ratio R_(U) is optimized aspreviously described, a curve 610 as illustrated in FIG. 20 may beproduced. The curve 610 has less-defined peaks 614 and valleys 616, andthus produces less variation of flow amplitude, and a more balancedinjection.

The partially exploded pump base 200 in FIG. 17 illustrates the internalmechanisms for linear (up and down) actuation of the saddle 206, whichis attached to a saddle stage 310. A motor 302 is controlled by acircuit board 304 and operated by the user interface 230 (FIG. 12 ),whose indicators 234 are lit by LEDs 306. The motor 302 turns a cam 316,in which includes a path 330. The saddle stage 310 has a pin 318extending from its back side. The pin 318 may be press fit, bonded orscrewed in place within the saddle stage 310. The saddle stage 310 issecured with screws to two slides 312, 314 through holes 326, 328, suchthat rotary motion of the cam 316 causes the pin 318 to track along thepath 330 of the cam 316, thus causing the saddle stage 310 attached tothe slides 312, 314 to slide upward and downward in cyclic motion. Theshape of the cam determines the amount of acceleration and decelerationin the motion. Upper posts 322 and lower posts 324 serve as guidesand/or stops of the saddle stage 310. The connector 114 of the pressuretransducer 106 for measuring vacuum may be plugged into socket 308 (alsoshown in FIG. 12 ), and pressure related signals may be processed by thecircuit board 304. The entire pump base 200 is reusable.

The inner contour diameter of the cam 316 may be sized and/or shaped tocontrol the stroke length of the piston 210 and the amount ofpulsatility (i.e., the difference between the high and low pressure). Insome cases, decreasing the stroke length decreases the amount ofpulsatility. In applications within the heart, such as coronary arteryapplications, lowering the amount of pulsatility can reduce theincidence of bradycardia. To compensate for a lower stroke length, andto maintain a sufficient total flow rate, the speed of the rotation ofthe cam (i.e. rotations per minute), can be increased, for example byincreasing motor output speed, either by gearing or by increased appliedvoltage.

Another embodiment of a system for aspirating thrombus 800 isillustrated in FIG. 21 . The system for aspirating thrombus 800includes, three major components: the pump base 200 of FIG. 12 , anaspiration catheter 818, and a tubing set 803. The aspiration catheter818 and the tubing set 803 represent disposable components 801, and thepump base 200 is a reusable component. It is not necessary to sterilizethe pump base 200 as it is kept in a non-sterile field or area duringuse. The aspiration catheter 818 and the tubing set 803 may each besupplied sterile, after sterilization by ethylene oxide gas, electronbeam, gamma, or other sterilization methods. The aspiration catheter 818may be packaged and supplied separately from the tubing set 803, or theaspiration catheter 818 and the tubing set 803 may be packaged togetherand supplied together. Alternatively, the aspiration catheter 818 andtubing set may be packaged separately, but supplied together (i.e.,bundled). As shown in FIGS. 21 and 22 . The aspiration catheter 818 andtubing set 803 share many of the same features as the aspirationcatheter 118 and tubing set 103 of FIG. 4 , but are configured to alloweasier separation from each other, and additional proceduraladaptability. The aspiration catheter 818 has a distal end 820comprising a guidewire tube 832 having a distal tip 836, and a proximalend 819 comprising a y-connector 810. The catheter shaft 842 of theaspiration catheter 818 is connected to the y-connector 810 via aprotective strain relief 856. In other embodiments, the catheter shaft842 may be attached to the y-connector 810 with a luer fitting. They-connector 810 may comprise a first female luer 851 which communicateswith a catheter supply lumen (as in the catheter 118 of FIGS. 4, 8-11 ),and a second female luer 855 which communicates with a catheteraspiration lumen (as in catheter 118 of FIGS. 4, 8-11 ).

Turning to FIG. 23 , the tubing set 803 is shown in more detail. A spike802 for coupling to a fluid source 20 (FIG. 1 ) allows fluid to enterthrough extension tubing 822 and a check valve 826, and into supply tube830. An optional injection port 828 allows injection of materials orremoval of air, as described in relation to previous embodiments. Acassette 816 is used in conjunction with the pump base 200, and issimilar in structure and function to the cassette 116 in FIGS. 15-16 .Fluid is pumped into injection tube 852 from cassette 816. A male luer854 is configured to attach to the female luer 851 of the y-connector810.

Returning to FIG. 21 , accessories 857 are illustrated that are intendedfor applying a vacuum source 22, including a syringe 849 having aplunger 867, to the catheter 818. The syringe 849 is attached to syringeextension tubing 859 via the luer 865 of the syringe 849. A stopcock 847may be used to hold maintain the vacuum, or the plunger 867 may be alocking variety of plunger. A luer 861 of the syringe extension tubing859 is connected to a pressure transducer 806, the pressure transducer806 having a male luer 863 for connection to a connector (e.g., femaleluer) 804 of vacuum line 808. A male luer 853 at the end of the vacuumline 808 may be detachably secured to the female luer 855 of they-connector 810 of the aspiration catheter 818. Signals from thepressure transducer 806 are carried through cable 812 to a connector814. The connector 814 is plugged into the socket 308 (FIG. 12 ) of thepump base 200. Pressure related signals may be processed by the circuitboard 304 of the pump base 200. The pressure transducer 806 may be powerfrom the pump base 200, via cable 812. The accessories 857 may also besupplied sterile to the user.

In use, the pump base 200 resides outside the sterile field. Becauseoperation of the pump base 200 may be controlled by the presence orabsence of a pressure, a user who is working in the sterile field mayturn the pump on or off without touching the non-sterile pump base 200.For example, the pump may be started by placing a vacuum on the system(e.g., pulling the plunger 867 of the syringe 849). The pump may in turnbe stopped by removing the vacuum on the system (unlocking the plunger867 of the syringe 849 and allowing to release, or opening the stopcock847). The syringe 849 or the combination syringe 849 and stopcock 847may act as a sterile on/off button of the pump base 200. Alternatively,the aspiration catheter 818 may be initially used without the pump base200, with only aspiration being applied to the aspiration lumen. If incertain cases, if the aspiration lumen becomes clogged, the distal end820 of the aspiration catheter 818 may be backed off of the thrombus,and the pump base 200 and tubing set 803 may be coupled to theaspiration catheter 818, to then operate with forced saline injection,for increased aspiration, and clear the aspiration lumen. This will alsohelp stop any thrombus that is blocking the aspiration lumen from beinginadvertently delivered into the blood vessel of the patient.

FIGS. 24 and 25 illustrate a saline pump drive unit 400 having acompletely disposable pump head 500. The saline pump drive unit 400 isconfigured to be usable with the catheters 16, 118 described herein, orother embodiments of aspiration systems comprising fluid injection. InFIG. 24 , a bottom case 402 and a top case 404 having a label 406 aresecured together with screws 408. Contained within the bottom case 402and top case 404 are a battery pack 410 and an electronic control module412. A battery cover 416 holds the battery pack 410 in place. In someembodiments, the battery pack 410 may supply a voltage of 18 Volts DC,but systems utilizing other voltages are possible. A user interface 414enables operation of the saline pump drive unit. A vacuum bottle sleeve418 may be used when a vacuum bottle is incorporated as the vacuumsource 22. A spike 420 is connectable to a fluid source 20, and fluidinjectate passes from the fluid source 20 through extension tubing 422to a disposable piston pump head 500. Saline may be primed through thesystem by an automatic priming (“self-priming”) system described hereinin relation to prior embodiments, or may be primed by gravity from asaline bag that is located (for example on an IV pole) above the rest ofthe system. A valve on the lowest portion of the system may be opened inorder to prime the entire system.

As illustrated in FIG. 25 , the disposable piston pump head 500 isconfigured to couple to a motor shaft 504 of a motor 502, that ispowered by the battery pack 410 of the saline pump drive unit 400. Amotor plate 506 and a main body 508 of the disposable piston pump head500 are secured to each other with screws 510, and hold the internalcomponents of the disposable piston pump head 500. First and secondfollower plates 512, 514 are held together with screws 516 and bosses518 extending from the first follower plate 512. The first and secondfollower plates 512, 514 rotatably hold a cam 520. The cam may beasymmetric (as illustrated) or alternatively may be symmetric. Theasymmetry may be incorporated in order to control the amount of noise inthe pump, the contours serving to customize the shape of the pressurewave, and of the function of the pump. First and second bushings 522,524 are rotatably held on first and second pins 526, 528. The pins 526,528 insert into cylindrical cavities 530, 532 in each of the followerplates 512, 514.

In use, a user attaches the disposable piston pump head 500 to the motor502 of the saline pump drive unit 400 by bringing the motor plate 506close to the motor shaft 504 so that a d-shaped hole 534 in the cam 520can be pressed over the d-shaped motor shaft 504. Alternatively, thed-shapes may be other non-circular shapes, including, but not limited toelliptical, oval, or rectangular. In operation the motor 502 turns themotor shaft 504, which in turn turns the cam 520. The cam 520 turns,forcing the bushings 522, 524 to push the first and second followerplates 512, 514 back and forth in a first direction 536 and a seconddirection 538. A saddle 544 is carried on the second follower plate 514,and a piston 210 may be coupled to the saddle 544 in the same manner asdescribed herein with other embodiments. A supply cylinder 552 and aninjection cylinder 554 in the main body 508 are analogous to the supplycylinder 252 and injection cylinder 254 of the cassette 116 of thesystem 100. The piston 210 of the cassette 116 may be used in thedisposable piston pump head 500. The labelled components related to thepiston 210 in FIG. 25 are similar to those described in relation to thepiston 210 in FIGS. 15 and 16 . The outer diameter of the cam 520 may besized and/or shaped to control the stroke length of the piston 210 andthe amount of pulsatility (i.e., the difference between the high and lowpressure). In some cases, decreasing the stroke length decreases theamount of pulsatility. In applications within the heart, such ascoronary artery applications, lowering the amount of pulsatility canreduce the incidence of bradycardia. To compensate for a lower strokelength, and to maintain a sufficient total flow rate, the speed of therotation of the cam (i.e. rotations per minute), can be increased, forexample by increasing motor output speed, either by gearing or byincreased applied voltage. A vacuum spike 546 is used for coupling tothe vacuum source 22, for example a vacuum bottle held within the vacuumbottle sleeve 418. A vacuum switch valve 540, which is activated againstthe bias of a spring 542, may be used to allow pump activation. Forexample, the electronic control module 412 may be configured to initiatethe operation of the motor 502 automatically when the vacuum switchvalve 540 sends a signal corresponding to movement of the vacuum switchvalve 540, which occurs when a significant vacuum is achieved. Thiscontrol may be instead of or in addition to control from a vacuumpressure transducer, such as pressure transducer 106. The turning on ofthe vacuum may thus be used to simultaneously turn on the motor 502, sothat a single input begins the operation of the saline pump drive unit400. Additionally, a vacuum source 22 may be controlled by theelectronic control module 412 (for example, by opening or closing asolenoid), when a minimum injectate pressure is measured by anadditional pressure transducer. For example, when a pressure of about0.62 megapascal (90 pounds per square inch) or greater is measured, thevacuum may be activated or communicated to the system. An advantage ofthe saline pump drive unit 400 is that the user is required only toassemble a single component onto the shaft 504 of the motor 502.

As previously described, the systems according to any of the embodimentsof the present invention may be configured such that active flow ofsaline (or other) injectate is not possible without concurrent vacuumbeing applied for aspiration. Also, the systems may be configured suchaspiration is not possible without saline (or other) injectate flow. Thesystems according to any of the embodiments of the present invention maybe configured such that current driving the pump (for example thecurrent driving the motor 302, 502) is monitored, or by any alternativemonitoring method, such that when a change in condition occurs, forexample, air in the injection system, or clogs in any of the catheterlumens or extension tubes, or leaks within the system, the system shutsdown, in order to avoid events such as injection of air into the bloodvessels, or catheter or system failure.

FIG. 26 illustrates an aspiration catheter 700 inserted within a bloodvessel 165. The aspiration catheter 700 includes a guidewire lumen 702secured to the distal end 704 of the aspiration catheter 700 whichallows the aspiration catheter 700 to be tracked over a guidewire 706. Asupply lumen 708 is secured within an aspiration lumen 710. The supplylumen 708 extends through a tapering tube 712. In some embodiments, thetapering tube 712 may be constructed of polyimide. In some embodiments,the tapering tube 712 may have a luminal inner diameter that tapers fromits proximal end to its distal end. For example, in some embodiments,the luminal inner diameter may taper from about 0.3937 mm (0.0155inches) to about 0.2794 mm (0.011 inches). The supply lumen 708 extendsgenerally parallel to the aspiration lumen 710, however a distal end 714of the tapering tube 712 curves towards an interior wall surface 716 ofthe aspiration lumen 710, thus allowing an open end 718 of the supplylumen 708 to act as an orifice for applying a spray pattern 720. Theopen end 718 of the supply lumen 708 may further promote a jet or sprayeffect by having an internal diameter that is less than about 0.203 mm(0.008 inches). In some embodiments, the open end 718 of the supplylumen 708 may have an internal diameter that is between about 0.076 mm(0.003 inches) and about 0.102 mm (0.004 inches). The center of the openend 718 orifice may in some embodiments be about 0.3302 mm (0.013inches) to about 0.4826 mm (0.019 inches) proximal to the most proximalportion 724 of the open distal end 722 of the aspiration lumen 710, asillustrated by distance Din FIG. 26 . The most distal portion 726 of theopen distal end 722 of the aspiration lumen 710 is slightly distal ofthe most proximal portion 724 in the embodiment illustrated, and thushas an angled skive, but the skive angle A_(s) is not severe. A skiveangle A_(s) of between about 75° and about 89°, or between about 80° andabout 85° may be used, in order to allow a large portion of thrombusbeing pulled into the open distal end 722 of the aspiration lumen 710 tobe struck by high velocity exiting jet (e.g. saline) flow, asillustrated with the spray pattern 720.

FIG. 27 illustrates the catheter 700 of FIG. 26 being utilized todeliver a drug 730 to a target site 732 within a blood vessel 165. Thetarget site 732 may include an atherosclerotic lesion 728 and/or athrombus 734. Whereas the aspiration of thrombus, as in FIG. 26 ,involves actively applying a vacuum (e.g., from a vacuum source) on theaspiration lumen 710, the drug delivery illustrated in FIG. 27 , thoughutilizing the same catheter 700, allows the metering of a fine,precision volume flow rate of drug 730 to be delivered into the vessel.This is achieved by having significantly less vacuum applied to theaspiration lumen 710, or no vacuum applied to the aspiration lumen. Theprecision metering in small, controlled volumes, provides efficient useof typically expensive drugs, with minimal wasted drug. In addition, therelatively small volume, or dead space, of the supply lumen 708, becauseof its relatively small diameter, assures that upon stopping theinfusion of a drug 730, very little volume of inadvertent injection iseven possible.

In some embodiments, the drug 730 may be delivered at body temperature.In other embodiments, the drug 730 may be warmed, and delivered at anelevated temperature, for example, to increase the activity andeffectiveness of a drug. This may be done, for example, to get a moreeffective dose, with a smaller volume of drug. In other embodiments, thedrug 730 may be cooled and delivered at a reduced temperature (i.e., inrelation to the body temperature). The drug 730 may be cooled to controlthe activity level, or to delay the activity of the drug (e.g., so thatit is active downstream, at a location that is not reachable by thecatheter 700). In some cases, the drug 730 may be cooled in order toapply a conjunctive therapeutic cooling effect on the tissue beingtreated. In some cases, the therapeutic cooling effect may be achievedfrom cooled saline or other aqueous non-drug media alone.

Some of the drugs 730 which may be delivered include thrombolytic agents(clot busting drugs), such as streptokinase, tissue plasminogenactivator (t-PA), recombinant or genetically-engineered tissueplasminogen activator, tenecteplase (TNK), urokinase, staphylokinase,and reteplase. Alternatively, stem cells or “cocktails” containing stemcells may be delivered. In some cases, glycoprotein inhibitors (GPI's)may be injected through the supply lumen 708 of the aspiration catheter700. Saline or other aqueous solutions may be delivered alone forselective dilution of blood at the target site 732. In someapplications, a solution may be used which is capable of exhibiting aphase change, for example, when its pressure or temperature is changed.In these applications, a liquid may be injected that becomes a gas whenexiting from a small orifice, for example at the open end 718 of thesupply lumen 708. Alternatively, a gas may be injected that becomes aliquid when being forced through a small orifice, such as the open end718 of the supply lumen 708. In any of the applications in which drugs730 or other materials are injected intravascularly through the catheter700, the injection of the drugs 730 or other materials may occur before,during, after, or instead of an aspiration procedure. Returning to theaspiration catheter 818 of FIGS. 21-22 , if, during an aspirationprocedure, it is desired to deliver drugs down the supply lumen and intothe vessel, the tubing set 803 may be removed from the aspirationcatheter 818 by disconnecting the male luer 854 of the tubing set 803from the female luer 851 of the aspiration catheter 818, and the drugmay be injected directly into the supply lumen at the female luer 851,for example, by a syringe or metering system, including asyringe/syringe pump combination. By also removing the vacuum sourcefrom the female luer 855 of the aspiration catheter 818, when aspirationlumen now serves as an overflow, so that the fluid being delivered intothe patient (e.g., intravascularly) is maintained at a controlled rate.The volume of the supply lumen is relatively very small, so only a smallvolume of drug is needed to fill the supply lumen, and thus reach thedistal top of the aspiration catheter 818. This, at the end of theprocedure, very little drug is wasted, or needs to be disposed, allowingfor a very cost-effective procedure.

In the embodiments described herein, a sterile fluid path is providedextending all the way from the fluid source 20 to the distal opening40/open distal end 158 of the catheter 16, 118. In both the embodimentsof the system 100 of FIGS. 4-17 , the system 800 of FIGS. 21-23 , andthe embodiments of FIGS. 24-25 , a disposable catheter and disposablepump set are configured to be supplied sterile, and coupled to anon-sterile (reusable) pump base 200 or pump motor 502. Thesecombinations allow for reusability of the more expensive components, andfor reusability (and maximized sterility) of the less expensivecomponents, thus maximizing cost containment and patient safety at thesame time. Turning to FIG. 61 , a system 1500 comprising an aspirationcatheter 1502 includes a first fluid source 1504 and a second fluidsource 1506. A tubing set 1508 having a first spike 1510 and secondspike 1512 is configured for coupling to the first interface 1514 of thefirst fluid source 1504 and the second interface 1516 of the secondfluid source 1506. The tubing set 1508 further comprises a y-fitting1518 for receiving fluid from the first fluid source 1504 and secondfluid source 1506 and passing it through the supply lumen 1520 of theaspiration catheter 1502. A first clamp 1522 may be used to open orclose the supply from the first fluid source 1504 and a second clamp1524 may be used to open or close the supply from the second fluidsource 1506. In a first condition, the first clamp 1522 is open and thesecond clamp 1524 is closed, and so only fluid from the first fluidsource 1504 is passed on to the supply lumen 1520 of the aspirationcatheter 1502. In a second condition, the first clamp 1522 is closed andthe second clamp 1524 is open, and so only fluid from the second fluidsource 1506 is passed on to the supply lumen 1520 of the aspirationcatheter 1502. In a third condition, the first clamp 1522 is open orpartially open and the second clamp 1524 is open or partially open, andso fluid from the first fluid source 1504 and fluid from the secondfluid source 1506 are passed on to the supply lumen 1520 of theaspiration catheter 1502. In some cases, the first fluid source 1504 maybe at a different temperature than the second fluid source 1506. Inother cases, the first fluid source 1504 may contain a different type offluid than the second fluid source 1506. In some embodiments, a PinnacleHigh Flow Y-adapter set (B/Braun, Bethlehem, Pa., USA) may be used tocouple to the first fluid source 1504 and the second fluid source 1506.

FIG. 28 illustrates an aspiration catheter 900 including a shaft 901having an aspiration lumen 902 and a supply tube 903 having a supplylumen 904 (high pressure lumen). The supply tube 903 is secured to aninner wall 906 of the shaft 901, for example, by adhesive, epoxy,mechanical securement, or thermal bonding or tacking. The supply lumen904 is configured to carry pressurized fluid 912, which may includesaline, lytic (thrombolytic) agents, contrast agents, or other agents.In use, the pressurized fluid 912 exits in a spray pattern 914 from anorifice 908 adjacent the distal end 910 of the supply lumen 904,impinging against an interior wall surface 916 of the aspiration lumen902. The agent or agents may be undiluted or may be diluted (e.g., withsaline). A jet spray impact 911 against the interior wall surface 916may form a distal component and/or a proximal component, as described infurther detail in FIGS. 32, 36, and 40 . The distal component orproximal component may be substantially distally-oriented orsubstantially proximally-oriented, in part or in whole, because offactors such as: the particular level of positive pressure of thepressurized fluid 912 within the supply lumen 904, or because of theparticular geometry of the orifice 908, or because of the particularlevel of negative pressure on the aspiration lumen 902, or because ofthe particular geometry of the interior wall surface 916, separately, orin any type of combination. A pump, syringe, or other source ofpressurization may be coupled to the proximal end of the supply lumen904, to allow pressurization or pulsation of the supply lumen 904. Insome embodiments, the pump base 200 (FIG. 12 ) may be used to supply andpressurize the supply lumen 904 with the fluid 912. The supply tube 903includes a plug 918 which blocks the end of the supply lumen 904,forcing pressurized fluid 912 through the orifice 908 and into theaspiration lumen 902, and, when operated to supply sufficient pressure,against the interior wall surface 916.

The spray pattern 914 may be directed by the orifice 908 toward theinterior wall surface 916 perpendicularly (i.e., at a 90° angle) 914 ain relation to the longitudinal axis 917 of the aspiration catheter 900and/or may impact the interior wall surface 916 at an oblique angle thatis distally-oriented 914 b or an oblique angle that isproximally-oriented 914 c. The spray pattern 914 may comprise two orthree of these elements 914 a, 914 b, 914 c together.

An alternative embodiment of an aspiration catheter 915 is illustratedin FIG. 29 , and includes a shaft 921 having an aspiration lumen 922 anda supply tube 923 having a supply lumen 924 (high pressure lumen). Thesupply tube 923 is secured to an inner wall 926 of the shaft 921. Thesupply lumen 924 is configured to carry pressurized fluid 912, which mayinclude saline, lytic (thrombolytic) agents, contrast agents, or otheragents. The agent or agents may be undiluted or may be diluted (e.g.,with saline). The pressurized fluid 912 exits in a spray pattern 919from an orifice 928 adjacent the distal end 920 of the supply lumen 924and impinges against an interior wall surface 909 of the aspirationlumen 922. The interior wall surface 909 includes an additional element929 (e.g., deflection element) which is configured for deflecting atleast a portion of the spray pattern 919 either proximally or distally.The deflection element 929 includes a forward ramp 927 and a reverseramp 925 which converge at a dividing line 931. The forward ramp 927 isconfigured to deflect at least a portion of the spray pattern 919distally and the reverse ramp 925 is configured to deflect at least aportion of the spray pattern 919 proximally. A jet spray impact againstthe interior wall surface 909 may include a distal component and/or aproximal component, as described in further detail in FIGS. 33 and 37 .In other embodiments, the interior wall surface 909 may simply be adeformation of a portion of the inner wall 926 itself. The deformationmay take the place of the deflection element 929 and thus act as thedeflection element 929. The deformation may be an angulation orformation of the distal end 907 of the aspiration catheter 900 thatcauses the inner wall 926 to have, for example, one or more ramps orangled, or curvilinear surfaces.

A distal component or proximal component may be substantiallydistally-oriented or substantially proximally-oriented in part or inwhole because of factors such as: the particular level of positivepressure of the pressurized fluid 912 within the supply lumen 924, orbecause of the particular geometry of the orifice 928, or because of theparticular level of negative pressure on the aspiration lumen 922, orbecause of the particular geometry of the interior wall surface 909,separately, or in any type of combination. A pump, syringe, or othersource of pressurization may be coupled to the proximal end of thesupply lumen 924, to allow pressurization or pulsation of the supplylumen 924. The supply tube 923 includes a plug 932 which blocks thedistal end 920 of the supply lumen 924, forcing pressurized fluid 912through the orifice 928 and into the aspiration lumen 922 and, whenoperated to supply sufficient pressure, against the interior wallsurface 909 comprising ramps 925, 927. In some embodiments, a portion ofthe spray pattern 919 that strikes the forward ramp 927 is deflecteddistally. In some embodiments, a portion of the spray pattern 919 thatstrikes the reverse ramp 925 is deflected proximally. In someembodiments, the specific amount of negative pressure being applied onthe aspiration lumen 922 (e.g., by a vacuum source) controls how much ofthe spray pattern 919 impinges upon each of the ramps 925, 927.

In the aspiration catheter 915 of FIG. 29 , the ramps 925, 927 of theelement 929 extend from the dividing line 931 in a linear fashion,wherein the effective inner radius of the aspiration lumen changeslinearly in relation to the longitudinal location along the ramp 925,927. In contrast, FIG. 30 illustrates an aspiration catheter 934 havingnon-linear ramps 942, 944 (e.g., curvilinear) extending between adividing line 933. The aspiration catheter 934 includes a shaft 935having an aspiration lumen 936 and a supply tube 937 having a supplylumen 938 (high pressure lumen). The aspiration catheter 934 furtherincludes a deflection element 940 with ramps 942, 944 that each includea concave contour 946, 948, such that the effective inner radius of theaspiration lumen changes non-linearly in relation to the longitudinallocation along the ramp 942, 944. In some embodiments, the deflectionelement 940 may be configured for directing and/or deflecting a spraypattern 947 (emanating from orifice 949) that is narrow and/or thatcomprises a jet. In other embodiments, the deflection element 929 of theaspiration catheter 915 of FIG. 29 may be configured for directingand/or deflecting a spray pattern 919 that is wider or whichsignificantly diverges or spreads.

FIG. 31 illustrates an aspiration catheter 950 which includes a shaft951 having an aspiration lumen 952 and a supply tube 953 having a supplylumen 954 (high pressure lumen). The aspiration catheter 950 furtherincludes a deflection element 956 with a single distally-oriented ramp958 which is configured to deflect at least a portion of a spray pattern960 emanating from an orifice 962 in a substantially distal direction.

FIG. 32 illustrates the aspiration catheter 900 of FIG. 28 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 32 illustrates the aspirationcatheter 900 in a first mode of operation configured to causesubstantial aspiration of thrombi 966. A venturi effect is created bythe spray pattern 914, which may comprise a jet. Suction is thus createdat the distal opening 968 of the aspiration lumen 902 causing thethrombi 966 to be aspirated into the aspiration lumen 902. In addition,an aspiration pressure (negative pressure) may be applied at a proximalend of the aspiration lumen 902 (e.g., with a vacuum source, such as asyringe, vacuum chamber or vacuum pump), thus maintaining the flow ofthe thrombi 966 through the aspiration lumen 902. The impingement of thespray pattern 914 of the pressurized fluid 912 against the interior wallsurface 916 of the aspiration lumen 902, opposite the orifice 908, mayalso macerate the thrombi 966 into smaller pieces 970 which can help tolower the effective viscosity of the composite fluid flowing through theaspiration lumen 902. By applying a significant vacuum/aspirationpressure on the proximal end of the aspiration lumen 902, the removal ofthrombi 966 and any smaller pieces 970 of thrombi 966 can be optimized.The spray pattern 914 is at least partially diverted into asubstantially proximally-oriented flow 955 after impingement upon theinterior wall surface 916.

FIG. 33 illustrates the aspiration catheter 915 of FIG. 29 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 33 illustrates the aspirationcatheter 915 in a first mode of operation configured to causesubstantial aspiration of thrombi 966. A venturi effect is created bythe spray pattern 919, which may comprise a jet. Suction is thus createdat the distal opening 972 of the aspiration lumen 922 causing thethrombi 966 to be aspirated into the aspiration lumen 922. In addition,an aspiration pressure (negative pressure) may be applied at a proximalend of the aspiration lumen 922 (e.g., with a vacuum source, such as asyringe, vacuum chamber or vacuum pump), thus maintaining the flow ofthe thrombi 966 through the aspiration lumen 922. The impingement of thespray pattern 919 of the pressurized fluid 912 against the reverse ramp925 of the deflection element 929, opposite the orifice 928, may alsomacerate the thrombi 966 into smaller pieces 970 which can help to lowerthe effective viscosity of the composite fluid flowing through theaspiration lumen 902. By applying a significant vacuum/aspirationpressure on the proximal end of the aspiration lumen 922, the removal ofthrombi 966 and any smaller pieces 970 of thrombi 966 can be optimized.The spray pattern 919 is at least partially diverted into asubstantially proximally-oriented flow 957 after impingement upon thereverse ramp 925 of the deflection element 929.

FIG. 34 illustrates the aspiration catheter 934 of FIG. 30 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 34 illustrates the aspirationcatheter 934 in a first mode of operation configured to causesubstantial aspiration of thrombi 966. A venturi effect is created bythe spray pattern 947, which may comprise a jet. Suction is thus createdat the distal opening 974 of the aspiration lumen 936 causing thethrombi 966 to be aspirated into the aspiration lumen 936. In addition,an aspiration pressure (negative pressure) may be applied at a proximalend of the aspiration lumen 936 (e.g., with a vacuum source, such as asyringe, vacuum chamber or vacuum pump), thus maintaining the flow ofthe thrombi 966 through the aspiration lumen 936. The impingement of thespray pattern 947 of the pressurized fluid 912 against the reverse ramp944 of the deflection element 940, opposite the orifice 949, may alsomacerate the thrombi 966 into smaller pieces 970 which can help to lowerthe effective viscosity of the composite fluid flowing through theaspiration lumen 936. By applying a significant vacuum/aspirationpressure on the proximal end of the aspiration lumen 936, the removal ofthrombi 966 and any smaller pieces 970 of thrombi 966 can be optimized.The spray pattern 947 is at least partially diverted into asubstantially proximally-oriented flow 959 after impingement upon thereverse ramp 944 of the deflection element 940.

FIG. 35 illustrates the aspiration catheter 950 of FIG. 31 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 35 illustrates the aspirationcatheter 950 in a first mode of operation configured to causesubstantial aspiration of thrombi 966. A venturi effect is created bythe spray pattern 960, which may comprise a jet. Suction is thus createdat the distal opening 976 of the aspiration lumen 952 causing thethrombi 966 to be aspirated into the aspiration lumen 952. In addition,an aspiration pressure (negative pressure) may be applied at a proximalend of the aspiration lumen 952 (e.g., with a vacuum source, such as asyringe, vacuum chamber or vacuum pump), thus maintaining the flow ofthe thrombi 966 through the aspiration lumen 952. The impingement of thespray pattern 960 of the pressurized fluid 912 against the interior wallsurface 978 which is proximal to the deflection element 956, oppositethe orifice 962, may also macerate the thrombi 966 into smaller pieces970 which can help to lower the effective viscosity of the compositefluid flowing through the aspiration lumen 952. By applying asignificant vacuum/aspiration pressure on the proximal end of theaspiration lumen 952, the removal of thrombi 966 and any smaller pieces970 of thrombi 966 can be optimized. The spray pattern 960 is at leastpartially diverted into a substantially proximally-oriented flow 961after impingement upon the interior wall surface 978 which is proximalto the deflection element 956.

FIG. 36 illustrates the aspiration catheter 900 of FIG. 28 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 36 illustrates the aspirationcatheter 900 in a second mode of operation configured to deliver a fluid(such as a fluid comprising an agent) distally out the distal opening968 of the aspiration lumen 902. The impingement of the spray pattern914 of the pressurized fluid 912 against the interior wall surface 916of the aspiration lumen 902, opposite the orifice 908, at leastpartially diverts the spray pattern 914 into a substantiallydistally-oriented flow 963. In addition, an aspiration pressure(negative pressure) may be reduced, completely stopped, or simply notapplied at a proximal end of the aspiration lumen 902, thus allowing atleast some of the spray pattern 914 to transform into the substantiallydistally-oriented flow 963 after impingement upon the interior wallsurface 916. In some embodiments, the orifice 908 and/or the interiorwall surface 916 may be configured such that in some conditions, thesubstantially distally-oriented flow 963 may itself be a jet. The agentmay comprise a lytic agent, such as a thrombolytic agent, or maycomprise a contrast agent. The substantially distally-oriented flow 963may comprise 50% or more of the spray pattern 914 (upon deflection), or60% or more, or 70% or more, or 80% or more, or 90% or more, or even100%.

FIG. 37 illustrates the aspiration catheter 915 of FIG. 29 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 37 illustrates the aspirationcatheter 915 in a second mode of operation configured to deliver a fluid(such as a fluid comprising an agent) distally out the distal opening972 of the aspiration lumen 922. The impingement of the spray pattern919 of the pressurized fluid 912 against the forward ramp 927 of thedeflection element 929, opposite the orifice 928, at least partiallydiverts the spray pattern 919 into a substantially distally-orientedflow 965. In addition, an aspiration pressure (negative pressure) may bereduced, completely stopped, or simply not applied at a proximal end ofthe aspiration lumen 922, thus allowing at least some of the spraypattern 919 to transform into the substantially distally-oriented flow965 after impingement upon the forward ramp 927 of the deflectionelement 929. In some embodiments, the orifice 928 and/or the forwardramp 927 of the deflection element 929 may be configured such that insome conditions, the substantially distally-oriented flow 965 may itselfbe a jet. The agent may comprise a lytic agent, such as a thrombolyticagent, or may comprise a contrast agent.

FIG. 38 illustrates the aspiration catheter 934 of FIG. 30 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 38 illustrates the aspirationcatheter 934 in a second mode of operation configured to deliver a fluid(such as a fluid comprising an agent) distally out the distal opening974 of the aspiration lumen 936. The impingement of the spray pattern947 of the pressurized fluid 912 against the forward ramp 942 of thedeflection element 940, opposite the orifice 949, at least partiallydiverts the spray pattern 947 into a substantially distally-orientedflow 967. In addition, an aspiration pressure (negative pressure) may bereduced, completely stopped, or simply not applied at a proximal end ofthe aspiration lumen 936, thus allowing at least some of the spraypattern 947 to transform into the substantially distally-oriented flow967 after impingement upon the forward ramp 942 of the deflectionelement 940. In some embodiments, the orifice 949 and/or the forwardramp 942 of the deflection element 940 may be configured such that insome conditions, the substantially distally-oriented flow 967 may itselfbe a jet. The agent may comprise a lytic agent, such as a thrombolyticagent, or may comprise a contrast agent.

FIG. 39 illustrates the aspiration catheter 950 of FIG. 31 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 39 illustrates the aspirationcatheter 950 in a second mode of operation configured to deliver a fluid(such as a fluid comprising an agent) distally out the distal opening976 of the aspiration lumen 952. The impingement of the spray pattern960 of the pressurized fluid 912 against the distally-oriented ramp 958of the deflection element 956, opposite the orifice 962, at leastpartially diverts the spray pattern 960 into a substantiallydistally-oriented flow 969. In addition, an aspiration pressure(negative pressure) may be reduced, completely stopped, or simply notapplied at a proximal end of the aspiration lumen 952, thus allowing atleast some of the spray pattern 960 to transform into the substantiallydistally-oriented flow 969 after impingement upon the distally-orientedramp 958 of the deflection element 956. In some embodiments, the orifice962 and/or the distally-oriented ramp 958 of the deflection element 956may be configured such that in some conditions, the substantiallydistally-oriented flow 969 may itself be a jet. The agent may comprise alytic agent, such as a thrombolytic agent, or may comprise a contrastagent.

The delivery of an agent comprising a drug using the second mode ofoperation described in FIGS. 36-39 in relation to aspiration catheters900, 915, 934, 950 may be achieved in a precise manner which allows forcorrect dosage, without wasting often-expensive drugs. The small innerdiameter of transverse internal dimension of the supply lumen 904, 924,938, 954 not only allows for precision and small volume introduction ofthe agent, but also avoids unwanted loss of agent when it is desired tosuddenly stop injection. This is a significant improvement overstandard, gravity-fed injection systems. In addition, the use of thepump base 200 (FIG. 12 ) to pressurize the supply lumen 904, 924, 938,954 to deliver the agent adds additional precision, control, and lack ofwaste. This decreases the cost of a procedure, increases the accuracy ofthe drug treatment (or, for example, contrast delivery), and may alsospeed up the procedure, because of fewer errors to correct or steps torepeat. This in itself may be another element for saving cost. Thoughthe word “aspiration” is used in defining the aspiration lumen 902, 922,936, 952 and the aspiration catheters 900, 915, 934, 950, it should beapparent that a user may choose to use the aspiration catheters 900,915, 934, 950 in the second mode only, as described in relation to FIGS.36-39 , and may in some cases choose to do so without any aspirationwhatsoever.

FIG. 40 illustrates the aspiration catheter 900 of FIG. 28 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 40 illustrates the aspirationcatheter 900 in a third mode of operation configured to deliver a fluid(such as a fluid comprising an agent) distally out the distal opening968 of the aspiration lumen 902 while also causing at least someaspiration of thrombi 966. The impingement of the spray pattern 914 ofthe pressurized fluid 912 against the interior wall surface 916 of theaspiration lumen 902, opposite the orifice 908, at least partiallysplits the spray pattern 914 into a substantially distally-oriented flow963 and a substantially proximally-oriented flow 955. An aspirationpressure (negative pressure) may be applied, adjusted, increased, orreduced at a proximal end of the aspiration lumen 902, thus allowing atleast some of the spray pattern 914 to transform into the substantiallydistally-oriented flow 963 after impingement upon the interior wallsurface 916 and at least some of the spray pattern 914 to transform intothe substantially proximally-oriented flow 955 after impingement uponthe interior wall surface 916. In some embodiments, the orifice 908and/or the interior wall surface 916 may be configured such that in someconditions, the substantially distally-oriented flow 963 may itself be ajet. The agent may comprise a lytic agent, such as a thrombolytic agent,or may comprise a contrast agent.

FIG. 41 illustrates the aspiration catheter 934 of FIG. 30 in use withina blood vessel 964 as part of an aspiration system 10 or system foraspirating thrombus 100, 800. FIG. 41 illustrates the aspirationcatheter 934 in a third mode of operation configured to deliver a fluid(such as a fluid comprising an agent) distally out the distal opening974 of the aspiration lumen 936 while also causing at least someaspiration of thrombi 966. The impingement of the spray pattern 947 ofthe pressurized fluid 912 against the ramps 942, 944 of the deflectionelement 940, opposite the orifice 949, at least partially splits thespray pattern 947 into a substantially distally-oriented flow 967 and asubstantially proximally-oriented flow 959. An aspiration pressure(negative pressure) may be applied, adjusted, increased, or reduced at aproximal end of the aspiration lumen 936, thus allowing at least some ofthe spray pattern 947 to transform into the substantiallydistally-oriented flow 967 after impingement upon the forward ramp 942of the deflection element 940 and at least some of the spray pattern 947to transform into the substantially proximally-oriented flow 959 afterimpingement upon the reverse ramp 944 of the deflection element 940. Insome embodiments, the orifice 949 and/or the forward ramp 942 of thedeflection element 940 may be configured such that in some conditions,the substantially distally-oriented flow 967 may itself be a jet. Theagent may comprise a lytic agent, such as a thrombolytic agent, or maycomprise a contrast agent.

FIG. 42 illustrates an aspiration catheter 1000 including a shaft 1001having an aspiration lumen 1002, a first supply tube 1003 having a firstsupply lumen 1004 and a second supply tube 1005 having a second supplylumen 1006. The first supply tube 1003 and second supply tube 1005 aresecured to an inner wall 1008 of the shaft 1001. The first supply lumen1004 is configured to carry pressurized fluid 912, which may includesaline, lytic (thrombolytic) agents, contrast agents, or other agents.The pressurized fluid 912 exits a first orifice 1010 of the first supplylumen 1004 in a spray pattern 1014 that is directed at an oblique,distally-oriented angle 1016 with respect to a longitudinal axis 1018 ofthe aspiration catheter 1000. The second supply lumen 1005 is configuredto carry pressurized fluid 912, which may include saline, lytic(thrombolytic) agents, contrast agents, or other agents. The pressurizedfluid 912 exits a second orifice 1020 of the second supply lumen 1006 ina spray pattern 1022 that is directed at an oblique, proximally-orientedangle 1024 with respect to the longitudinal axis 1018 of the aspirationcatheter 1000. The agent or agents may be undiluted or may be diluted(e.g., with saline).

A first curved hollow tip extension 1026 includes an outer diameter atits proximal end 1012 that is inserted within the first supply lumen1004 of the first supply tube 1003. The curve of the first curved hollowtip extension 1026 aims the spray pattern 1014 that exits the firstorifice 1010 in the oblique, distally-oriented angle 1016 such that asubstantially distally-oriented flow 1028 is directed, or oriented,outside the open distal end 1030 of the aspiration lumen 1002. A secondcurved hollow tip extension 1032 includes an outer diameter at itsproximal end 1034 that is inserted within the second supply lumen 1006of the second supply tube 1005. The curve of the second curved hollowtip extension 1032 aims the spray pattern 1022 that exits the secondorifice 1020 in the oblique, proximally-oriented angle 1024 such that asubstantially proximally-oriented flow 1038 is oriented towards an innerwall surface 1040 the aspiration lumen 1002. The application andadjustment of a negative pressure on a proximal end of the aspirationlumen 1002 may be used to adjust the extent of aspiration (e.g., ofthrombus or blood) and the extent of delivery of an agent distallythrough the first orifice 1010.

FIG. 43 illustrates an aspiration catheter 1050 including a shaft 1051having an aspiration lumen 1052, and a first supply tube 1053 having afirst supply lumen 1054. The first supply tube 1053 bifurcates into afirst tubular branch 1046 having a first branch lumen 1047 and a secondtubular branch 1048 having a second branch lumen 1049. The first tubularbranch 1046 and second tubular branch 1048 are secured to an inner wall1056 of the shaft 1051. The first supply lumen 1054, first tubularbranch 1046, and second tubular branch 1048 are configured to carrypressurized fluid 912, which may include saline, lytic (thrombolytic)agents, contrast agents, or other agents. The pressurized fluid 912exits a first orifice 1058 of the first branch lumen 1047 in a spraypattern 1060 that is directed at an oblique, distally-oriented angle1062 with respect to a longitudinal axis 1064 of the aspiration catheter1050. The pressurized fluid 912 exits a second orifice 1066 of thesecond branch lumen 1049 in a spray pattern 1068 that is directed at anoblique, proximally-oriented angle 1070 with respect to the longitudinalaxis 1064 of the aspiration catheter 1050. The agent or agents may beundiluted or may be diluted (e.g., with saline). One or more deflectionmembers 1072 having one or more ramps 1074, 1076 (e.g., forward ramp1074 and reverse ramp 1076) may be carried on an inner wall 1078 of theaspiration lumen 1052 for deflecting one or both spray patterns 1060,1068 to produce a distally-oriented flow 1080 and/or proximally-orientedflow 1082. In other embodiments, the forward ramp 1074 and/or reverseramp 1076 may simply be projections of the inner wall 1078, or may beformed by a deflection of the shaft 1001.

FIG. 44A illustrates a catheter 1200 having a shaft 1202 having a lumen1203 and a supply tube 1204 having a supply lumen 1206. The supply tube1204 is secured to an inner wall 1208 of the shaft 1202 and includes anorifice 1210 configured for directing pressurized fluid to exit in aspray pattern 1212, which may form a jet. The spray pattern 1212 isdirected against an opposing deflection member 1214 which may either bea separate component secured to the inner wall 1208 of the shaft 1202,or may be a formed portion of the shaft 1202. The lumen 1204 is aguidewire lumen configured for allowing the catheter 1200 to track overthe guidewire (not shown). In use, the catheter 1200 is operated as aninfusion catheter, and the guidewire may be retracted proximally to theorifice 1210 and deflection member 1214 so that they are able tofunction with less potential interference. In some cases, the guidewiremay be removed entirely. In other embodiments, the lumen 1204 may be anaspiration lumen, configured for aspiration of material such as thrombusor other emboli. The lumen may alternatively have other purposes, forexample as a conduit for larger volume injections or infusions. Thedeflection member 1214 has a flat surface extending transversely, orradially and is configured to deflect the spray pattern 1212. Forexample, the deflection member 1214 may be configured to deflect thespray pattern 1212 so that at least some of an agent carried by thespray pattern 1212 is urged out of the distal opening 1215 of the lumen1204.

FIG. 44B illustrates a catheter 1216 including a shaft 1218 having alumen 1220 and a supply tube 1222 having a supply lumen 1224. The supplytube 1222 is secured to an inner wall 1226 of the shaft 1218 andincludes an orifice 1228 configured for directing pressurized fluid toexit in a spray pattern 1230, which may form a jet. The spray pattern1230 is directed against an opposing deflection member 1232 which mayeither be a separate component secured to the inner wall 1226 of theshaft 1218, or may be a formed portion of the shaft 1218. The lumen1220, like the lumen 1203 of the catheter 1200 of FIG. 44A, may be aguidewire lumen and/or an aspiration lumen, or may have other purposes.The deflection member 1232 has a flat surface extending longitudinally,or axially, and is configured to deflect the spray pattern 1230. Forexample, the deflection member 1232 may be configured to deflect thespray pattern 1230 so that at least some of an agent carried by thespray pattern 1230 is urged out of the distal opening 1234 of the lumen1220.

FIG. 45A illustrates a catheter 1236 having a shaft 1238 having a lumen1240 and a supply tube 1242 having a supply lumen 1244. The supply tube1242 is secured to an inner wall 1246 of the shaft 1238 and includes anorifice 1248 configured for directing pressurized fluid to exit in aspray pattern 1250, which may form a jet. The spray pattern 1250 isdirected against an opposing deflection member 1252 which may either bea separate component secured to the inner wall 1246 of the shaft 1238,or may be a formed portion of the shaft 1238. The lumen 1240 is aguidewire lumen configured for allowing the catheter 1236 to track overthe guidewire (not shown). In use, the catheter 1236 is operated as aninfusion catheter, and the guidewire may be retracted proximally to theorifice 1248 and deflection member 1252 so that they are able tofunction with less potential interference. In some cases, the guidewiremay be removed entirely. In other embodiments, the lumen 1240 may be anaspiration lumen, configured for aspiration of material such as thrombusor other emboli. The lumen may alternatively have other purposes, forexample as a conduit for larger volume injections or infusions. Thedeflection member 1252 has a convex surface when viewed from an endview, and is configured to deflect the spray pattern 1250. For example,the deflection member 1252 may be configured to deflect the spraypattern 1250 so that at least some of an agent carried by the spraypattern 1250 is urged out of the distal opening 1254 of the lumen 1240.

FIG. 45B illustrates a catheter 1256 including a shaft 1258 having alumen 1260 and a supply tube 1262 having a supply lumen 1264. The supplytube 1262 is secured to an inner wall 1266 of the shaft 1258 andincludes an orifice 1268 configured for directing pressurized fluid toexit in a spray pattern 1270, which may form a jet. The spray pattern1270 is directed against an opposing deflection member 1272 which mayeither be a separate component secured to the inner wall 1266 of theshaft 1258, or may be a formed portion of the shaft 1258. The lumen 1260may be a guidewire lumen and/or an aspiration lumen, or may have otherpurposes. The deflection member 1272 has a convex surface when viewedfrom the side, and is configured to deflect the spray pattern 1270. Forexample, the deflection member 1272 may be configured to deflect thespray pattern 1270 so that at least some of an agent carried by thespray pattern 1270 is urged out of the distal opening 1274 of the lumen1260.

FIG. 63 illustrates a catheter 1656 including a shaft 1658 having alumen 1660 and a supply tube 1662 having a supply lumen 1664. The supplytube 1662 is secured to an inner wall 1666 of the shaft 1658 andincludes an orifice 1668 configured for directing pressurized fluid toexit in a spray pattern 1670, which may form a jet. The spray pattern1670 is directed against an opposing deflection member 1672 which mayeither be a separate component secured to the inner wall 1666 of theshaft 1658, or may be a formed portion of the shaft 1658. The lumen 1660may be a guidewire lumen and/or an aspiration lumen, or may have otherpurposes. The deflection member 1672 has a sloped surface when viewedfrom the side, and is configured to deflect the spray pattern 1670substantially distally such that it is urged out of the distal opening1674 of the lumen 1660. The deflection member 1672, when formed as aseparate component, may comprise a metallic component or a polymericcomponent.

FIG. 64 illustrates a catheter 1756 including a shaft 1758 having alumen 1760 and a supply tube 1762 having a supply lumen 1764. The supplytube 1762 is secured to an inner wall 1766 of the shaft 1758 andincludes an orifice 1768 configured for directing pressurized fluid toexit in a spray pattern 1770, which may form a jet. The spray pattern1770 is directed against an opposing deflection member 1772 which mayeither be a separate component secured to the inner wall 1766 of theshaft 1758, or may be a formed portion of the shaft 1758. The lumen 1760may be a guidewire lumen and/or an aspiration lumen, or may have otherpurposes. The deflection member 1772 has a sloped surface when viewedfrom the side, and is configured to deflect the spray pattern 1770substantially proximally. The deflection member 1772, when formed as aseparate component, may comprise a metallic component or a polymericcomponent.

FIGS. 46A and 46B illustrate a catheter 1276 having a shaft 1278 havinga lumen 1280 and a supply tube 1282 having a supply lumen 1284. Thesupply tube 1282 is secured to an inner wall 1286 of the shaft 1278 andincludes an orifice 1288 configured for directing pressurized fluid toexit in a spray pattern 1290, which may form a jet. The spray pattern1290 is directed against an opposing adjustable deflection member 1292having at least two states, a first state (FIG. 46A) and a second state(FIG. 46B). In the embodiment shown, the adjustable deflection member1292 comprises a balloon secured to the inner wall 1286 of the shaft1278 such that it may be inflated or deflated via a fluid passage 1294within or carried by the shaft 1278. An inflation device with or withouta volume measurement device, pressure sensor, and/or pressure gauge maybe coupled to a proximal end of the fluid passage 1294, to thus aid inthe inflation or deflation of the balloon. The lumen 1280 is a guidewirelumen, configured for allowing the catheter 1276 to track over theguidewire (not shown). In use, the catheter 1276 is operated as aninfusion catheter, and the guidewire may be retracted proximally to theorifice 1288 and adjustable deflection member 1292 so that they are ableto function with less potential interference. In some cases, theguidewire may be removed entirely. In other embodiments, the lumen 1280may be an aspiration lumen, configured for aspiration of material suchas thrombus or other emboli. The lumen may alternatively have otherpurposes, for example as a conduit for larger volume injections orinfusions.

The adjustable deflection member 1292, in at least one of its two ormore states, is configured to deflect the spray pattern 1290. Forexample, the adjustable deflection member 1292 may be configured todeflect the spray pattern 1290 so that at least some of an agent carriedby the spray pattern 1290 is urged out of the distal opening 1296 of thelumen 1280. In a first state displayed in FIG. 46A, the adjustabledeflection member 1292 is deflated, or in other words, its interiorvolume 1298 is substantially empty. This first state may be desired if,for example, passing the catheter 1276 over a guidewire that extendsthrough the lumen 1280, or if aspirating through the lumen 1280 (with orwithout the guidewire in place). In another version of the first state,a vacuum (negative pressure) may additionally be placed and held on thefluid passage 1294 (e.g., from an evacuated syringe or evacuated lockingsyringe on the proximal end of the fluid passage 1294) to minimize theprofile of the deflated adjustable deflection member 1292 and thusmaximize the cross-sectional area of the lumen 1280 in this area. In asecond state displayed in FIG. 46B, fluid has been injected through thefluid passage 1294 (e.g., by a syringe or other type of inflationdevice) and into the interior volume 1298 of the adjustable deflectionmember 1292 through an aperture 1299 between the fluid passage 1294 andthe interior volume 1298. The adjustable deflection member 1292 in itssecond state is configured to deflect the spray pattern 1290 in adesired direction, such as at least partially out through the distalopening 1296 of the lumen 1280. The shape of the inflated adjustabledeflection member 1292 is depicted in FIG. 46B as having a convexnature, but in other embodiments, the balloon or other structureconstituting the adjustable deflection member 1292 may be fabricated toform one or more linear ramps, or other shapes. In addition, there maybe several different shapes or sizes that may be achieved by adjustingthe adjustable deflection member 1292 into several different states, byinjecting different volumes of fluid into the interior volume 1298.During fabrication, the shape of the adjustable deflection member 1292may be heat formed by use of one or more molds or fixtures. Anadditional state may even be possible, wherein the adjustable deflectionmember 1292 in inflated enough to substantially or completely block offthe lumen 1280, or to partially or completely block the orifice 1288.This additional state may be desired, for example, in cases during whichan embolus is aspirated into the catheter, and it is desired to maintainthe embolus within the catheter 1276 securely, while removing thecatheter 1276 from the patient.

FIG. 47 illustrates a supply tube 1300 having a lumen 1302, a wall 1304,and an orifice 1306 through the wall 1304. A spray pattern 1308 exitingthe orifice 1306, emanating from pressurized fluid within the lumen1302, has a substantially solid or straight stream, wherein the width(or diameter) W of the stream does not significantly increase. FIG. 48illustrates a supply tube 1310 having a lumen 1312, a wall 1314, and anorifice 1316 through the wall 1314. A spray pattern 1318 exiting theorifice 1316, emanating from pressurized fluid within the lumen 1312,has a divergent stream having an included angle x. FIG. 49 illustrates athree-dimensional depiction of a spray pattern 1320 having a divergentstream, which thus gives the spray pattern 1320 a conical shape 1322.

FIG. 50 illustrates a supply tube 1324 having a lumen 1326, a wall 1328,and an orifice 1330 through the wall 1328. A spray pattern 1332 exitingthe orifice 1330, emanating from pressurized fluid within the lumen1326, has a stream having a hollow conical shape 1334. FIG. 51illustrates a supply tube 1336 having a lumen 1338, a wall 1340, and arectangular orifice 1342 through the wall 1340. A spray pattern 1344exiting the rectangular orifice 1342, emanating from pressurized fluidwithin the lumen 1338, has a stream having a divergent wedge shape 1346.

FIG. 52 illustrates a supply tube 1348 having a lumen 1350, a wall 1352,and an orifice 1354 through the wall 1352. A spray pattern 1356 exitingthe orifice 1354, emanating from pressurized fluid within the lumen1350, has a directional vector V that is angled at an angle y withrespect to an axis AO of the orifice 1354. The directional vectorrepresents a central portion of the spray pattern 1356. The spraypattern 1356 diverges and has an included angle x. The spray pattern hasa distal-most extremity 1355 and a proximal-most extremity 1357. Thedistal-most extremity 1355 forms an angle z_(D) with the axis AO of theorifice 1354 and the proximal-most extremity 1357 forms an angle z_(P)with the axis AO of the orifice 1354. In other embodiments, the spraypattern 1356 may have a shape similar to any of the spray patterns 1308,1318, 1320, 1332, 1344 of FIGS. 47-51 , or any other shape.

Any of the shapes of the spray patterns 1308, 1318, 1320, 1332, 1344,1356 may be tailored by modifying the structure of the orifice in thewall of the supply tube (transverse dimension, diameter, length or wallthickness, angle, taper angle, cross-sectional shape), which facilitatesthe spray pattern(s) interfacing with the interior wall surface 916,1040, 1078 or deflection elements/members 929, 940, 956, 1072, 1214,1232, 1252, 1272, 1292 to create a number of different flow shapes,including substantially distally-oriented flow and/or substantiallyproximally-oriented flow. The spray patterns 1308, 1318, 1320, 1332,1344, 1356 may be tailored to comprise a jet, a stream, a mist, or otherspray physical characteristics. The spray patterns 1308, 1318, 1320,1332, 1344, 1356 may be convertible between any of these different modesor shapes with the aid of varying the pressure of the pressurized fluid.

FIG. 53 illustrates an aspiration catheter 1360 which has been insertedinto a blood vessel 1362 (artery, vein, etc.) and advanced such that theopen distal end 1364 of the aspiration lumen 1366 is adjacent athrombus/clot 1368. The aspiration catheter 1360 also includes a supplytube 1370 having a supply lumen 1372, and a guiding tube 1374 having aguidewire lumen 1376 configured for tracking over a guidewire 1378. Adilute or nondilute contrast media is pressurized by syringe, pump orother means through the supply lumen 1372 such that it exits the orifice1380 at the distal end 1382 of the supply lumen 1372. A jet spray 1384may include a distal component and/or a proximal component. The distalcomponent 1386 (FIG. 54 ) may be a substantially distally-orientedcomponent, and may at least partially exit the open distal end 1364 ofthe aspiration lumen 1366. The distal component 1386, as it fills avolume around the thrombus/clot 1368 (FIG. 54 ), may be viewed underradiography or fluoroscopy to identify a boundary 1388 of thethrombus/clot 1368. If the boundary 1388 is located within a desiredproximity to the open distal end 1364 the aspiration lumen 1366 of theaspiration catheter 1360, the user may desire to inject or pump (e.g.,with syringe or pump), using a high pressure, through the supply lumen1372, to start or to continue a thrombolysis procedure. In some cases,the user may use the dilute or non-dilute contrast media to perform thethrombolysis procedure. In some cases, the dilute or non-dilute contrastmedia may be combined or mixed with a lytic agent. In other cases, theuser may replace the dilute or non-dilute contrast media with saline ora lytic agent, for example, by priming the supply lumen. If instead theboundary 1388 is located distal to the open distal end 1364 of theaspiration lumen 1366 of the aspiration catheter 1360 by more than adesired amount, the user may choose to advance the aspiration catheter1360 until the open distal end 1364 is within the desired proximity tothe boundary 1388 of the thrombus/clot 1368. In some cases, the desiredproximity may be when the open distal end 1364 is flush with theboundary 1388 of the thrombus/clot 1368. In some cases, the desiredproximity may be when the open distal end 1364 is about one mm from theboundary 1388 of the thrombus/clot 1368. In some cases, the desiredproximity may be when the open distal end 1364 is about five mm from theboundary 1388 of the thrombus/clot 1368. Once the user advances theaspiration catheter 1360 such that the open distal end 1364 is withinthe desired proximity of the boundary 1688 of the thrombus/clot 1368,the user may start or continue the thrombolysis procedure.

FIG. 55 illustrates a method in which a user continually or temporarilyinjects or “puffs” small amounts 1396 of contrast agent (or contrastagent mixtures as described), in order to continually delineate theboundary 1388 of the thrombus/clot 1368, and the proximity of the opendistal end 1364 of the aspiration lumen 1366 of the aspiration catheter1360. In any of the embodiments presented herein, the distal end 1390 ofthe aspiration catheter 1360 may comprise a radiopaque marker or markerband 1392. In some embodiments, the catheter tubing 1394 may beradiopaque tubing, comprising radiopaque materials, including, but notlimited to barium-sulfate, tantalum oxide, or titanium oxide.

FIG. 56 illustrates a catheter system 1400 comprising a catheter 1402having a supply lumen 1404, and lumen 1406. A wall 1410 surrounding thesupply lumen 1404 includes an orifice 1408. A mandrel 1412 having aproximal end 1414 and a distal end 1416 extends through the lumen 1406.The distal end 1416 may have a curved portion 1418 (or hook portion)that includes a concavity 1420 for engaging a wall 1422 of the catheter1402. The mandrel 1412 may be configured for insertion through the lumen1406 such that the concavity 1420 engages the distal end 1424 of thewall 1422 (e.g., at the open distal end 1426) in a manner that traction(arrow, FIG. 57 ) may be placed by a user on the mandrel 1412, therebypulling the distal end 1428 of the catheter 1402 in a proximaldirection. This traction, coupled with the column strength of thecatheter 1402, causes the distal end 1428 of the catheter 1402 to flex,as shown in FIG. 57 . In some cases, the amount of flexure may becontrolled by a particular force applied on the proximal end 1414 of themandrel 1412 (e.g., by hand, or by a grasping tool which is connected tothe proximal end 1414 by a collet or other lock), such that the jet offluid 1430 exiting the orifice 1408 is steered such that it impinges onan adjacent structure (such as a thrombus/clot 1432). In someembodiments, the lumen 1406 may serve as an aspiration lumen, accordingto other embodiments described herein, and may also be used to aspirateat least some of the thrombus 1432. In this embodiment, the mandrel 1412may also be used to disengage the lumen 1406 from a thrombus 1432, incases where the thrombus 1432 becomes engaged, via vacuum, with the opendistal end 1426 of the lumen 1406. Contrast media may be added to thefluid being delivered through the supply lumen 1404, in order to bettervisualize the location and status of the thrombus 1432. Contrast mediamay even be delivered through the lumen 1406, if the lumen 1406 is notactively being used to aspirate. A user may flex the distal end 1428 ofthe catheter 1402 back and forth such that the jet of fluid 1430disrupts various areas/regions of the thrombus 1432. Additionally, theuser applies a vacuum to the lumen 1406 to remove disrupted/maceratedthrombus from the blood vessel 1362. A more thorough and efficientremoval of the thrombus 1432 is thus possible.

FIG. 58 illustrates a catheter system 1434 having most of thecharacteristics of the catheter system 1400 of FIGS. 56 and 57 , butwith an additional preformed shape. A mandrel 1436 is configured to flexthe distal end 1438 of the catheter 1440, but the distal end 1438 of thecatheter 1440 additionally has a preformed curve 1442. Thus, a largeflexure angle F range is possible, allowing the jet 1444 itself tostrike a thrombus with many different possible trajectories. FIG. 62illustrates a catheter system 1530 which combines the controlled flexureof the catheter system 1434 of FIG. 58 with internal deflection of ajet. A catheter 1532 includes a lumen 1534, a supply tube 1536 having asupply lumen 1538, and a tension mandrel 1540. The supply lumen 1538terminates at its distal end 1542 in an orifice 1544. In a firstflexural state (above), a jet 1546 deflects from a first point 1548 onthe inner wall 1550 and deflects in a first substantiallydistally-oriented flow 1552. In a second flexural state (below), a jet1554 deflects from a second point 1556 on the inner wall 1550 anddeflects in a second substantially distally-oriented flow 1558. Becausethe first substantially distally-oriented flow 1552 and the secondsubstantially distally-oriented flow 1558 are oriented in differentvectors, the steering of a distal jet or flow is possible by controlledtraction on the tension mandrel 1540. Thus, for the catheter system 1434of FIG. 58 and the catheter system 1530 of FIG. 62 allow for thesteering of a distally-oriented flow or jet, but by different cathetermeans.

FIGS. 59A and 59B illustrate an aspiration system 1450 comprising anaspiration catheter 1452 having a supply lumen 1454, an aspiration lumen1456 and an orifice 1458 communicating between the supply lumen 1454 andthe aspiration lumen 1456, and a mandrel 1460 having a proximal end 1462and a distal end 1464, the distal end 1464 including an enlarged portion1466. The enlarged portion 1466 of the mandrel 1460 may include a hook(e.g., shepherd's crook), a curve, or other structure which is effectivein disrupting a thrombus 1468 when the mandrel 1460 (and thus theenlarged portion 1466) is made to rotate 1470 and/or to longitudinallytranslate 1472. The mandrel 1460 may be inserted through the aspirationlumen 1456 of the aspiration catheter 1452 and may be rotated byattaching the proximal end 1462 of the mandrel 1460 to a rotation device1474. The rotation device 1474 may also translate the mandrel 1460back-and-forth longitudinally. The rotation device 1474 may includecomprise such devices as a SPINR™ device marketed by Merit MedicalSystems, Inc., (South Jordan, Utah, USA) or a FireBow™ device marketedby Vesatek, LLC (Irvine, Calif., USA). The enlarged portion 1466 may beused to disrupt a fibrous and/or calcified cap 1476 at one end of athrombus 1468 by applying a disruptive force through rotation and/orcyclic longitudinal displacement. A convex or blunt portion 1478 of theenlarged portion 1466 may form an atraumatic end to the mandrel 1460.The rotation device 1474 comprises a handle 1480, a motor 1482, arotatable chuck or lock 1484, and a transmission 1486 that is configuredto couple movement from the motor into movement (e.g., rotation and/orlongitudinal translation) of the rotatable chuck or lock 1484. Thetransmission 1486 may in some embodiments include gearing. A switch 1488may be pressed by a user while the user holds the handle 1480, to turnthe rotation/movement on or off. In some embodiments, the mandrel 1460may also be usable in the manner of the mandrel 1412 of FIGS. 56 and 57or the mandrel 1436 of FIG. 58 .

FIG. 60 illustrates a system for removing intracranial thrombus orintracranial hematoma (illustrated simply as BC-blood clots) through awindow, aperture, or hole in the cranium of a patient. The window,aperture, or hole may be made by any suitable device, including, but notlimited to a hand drill having a burr or other cutting element.Referring to FIG. 60 , a trocar 1156, for example a four-channel trocar,can be introduced through an introducer 1100 close to the treatment areawhere blood clots BC are located. A visualization device 1158 such as ascope device, including but not limited to the NeuroPen (Medtronic Inc.)or the Epic Microvision (Codman, J&J Company, Piscataway, N.J.), may beintroduced in the visualization channel of the trocar 1156, and anultrasound device 1112 may be introduced into the working channel of thetrocar 1156. The ultrasound device 1112 may transmit, for example, atfrequencies between about 1 kHz and about 20 MHz, and may be configuredto disrupt or break up the blood clot BC.

FIG. 60 shows a cross sectional view of a human skull and brain, showingan introducer 1100 placed through the aperture in the skull. The trocardevice 1156 is placed through the introducer 1100 and positioned withinthe treatment area where blood clots BC are located. The middle cerebralartery MCA is also shown. Often, the trocar 1156 can be introduceddirectly into the aperture in the skull without use of the introducer1100. A visualization device 1158 may be introduced through thevisualization channel of the trocar 1156. The visualization device 1158is connected to a monitor (not shown) through a cable 1159. Somevisualization devices (such as scopes) have an ocular element that canbe used for visualization instead of a monitor. An ultrasound device1112 having a handle 1157 is introduced through the working channel ofthe trocar 1156. Before the procedure, the physician directs the trocar1156 under the visualization device 1158 to the location of the bloodclots BC, and then positions the distal end of the ultrasound device1112 inside the blood clots and activates ultrasound energy delivery.The physician has the ability to simultaneously observe the field oftherapy with a visualization device 1158 while the therapeutic device1112 dissolves and aspirates blood clots from the patient's head. Bloodclots maybe aspirated through an irrigation or overflow channel, whichis analogous to the aspiration lumens of the aspiration cathetersdescribed herein. Also, blood clots may be aspirated through theultrasound device 1112. Suitable systems for removing intracranialthrombus or intracranial hematoma are described by Nita in U.S. PatentApplication Publication No. 2012/0330196, published Dec. 27, 2012, andtitled Method and Apparatus for Removing Blood Clots and Tissue from thePatient's Head, which is hereby incorporated by reference in itsentirety for all purposes.

To further improve the ability to dissolve blood clots BC, delivery ofone or more pharmacologic agents or microbubbles or nanobubbles to theclot location may be helpful. Such pharmacologic agents, microbubbles ornanobubbles can be delivered directly or in mixture with a conventionalsaline to the treatment location.

Cerebral temperature has been recognized as a strong factor in ischemicbrain damage. Clinical evidence has shown that hypothermia amelioratesbrain damage. Also, a therapeutic cooling to between 30° C. or 35° C.that includes the patient head or a whole body (systemic cooling) mayreduce ischemic brain damage; reduce intracranial pressure and edemaafter ICH. Focused cranial cooling can be achieved with a simple methodof placing ice or cold gel packs around the head or neck. Systemiccooling maybe be done by infusing ice-cold saline using intravenous (IV)approach.

Any of the embodiments described herein may be used in conjunction withthe Apollo™ System (Penumbra, Inc., Alameda, Calif., USA).

In some cases, parts or all of the devices described herein may be dopedwith, made of, coated with, or otherwise include a radiopaque material.Radiopaque materials are understood to be materials capable of producinga relatively bright image on a fluoroscopy screen or another imagingtechnique during a medical procedure. Some examples of radiopaquematerials can include, but are not limited to, gold, platinum,palladium, tantalum, tungsten alloy, polymer material loaded with aradiopaque filler, and the like. One or more hydrophilic or hydrophobiclubricious coatings may be used in order to improve trackability of theaspiration catheter 118 through the blood vessels.

In some instances, a degree of MRI compatibility may be imparted intoparts of the devices described herein. For example, to enhancecompatibility with Magnetic Resonance Imaging (MRI) machines, it may bedesirable to make various portions of the devices described herein frommaterials that do not substantially distort MRI images or causesubstantial artifacts (gaps in the images). Some ferromagneticmaterials, for example, may not be suitable as they may create artifactsin an MRI image. In some cases, the devices described herein may includematerials that the MRI machine can image. Some materials that exhibitthese characteristics include, for example, tungsten,cobalt-chromium-molybdenum alloys (e.g., UNS: R30003 such as ELGILOY®,PHYNOX®, and the like), nickel-cobalt-chromium-molybdenum alloys (e.g.,UNS: R30035 such as MP35-N® and the like), nitinol, and the like, andothers.

In some instances, some of the devices described herein may include acoating such as a lubricious coating or a hydrophilic coating.Hydrophobic coatings such as fluoropolymers provide a dry lubricity.Lubricious coatings improve steerability and improve lesion crossingcapability. Suitable lubricious polymers are well known in the art andmay include silicone and the like, hydrophilic polymers such ashigh-density polyethylene (HDPE), polytetrafluoroethylene (PTFE),polyarylene oxides, polyvinylpyrrolidones, polyvinylalcohols, hydroxyalkyl cellulosics, algins, saccharides, caprolactones, and the like, andmixtures and combinations thereof. Hydrophilic polymers may be blendedamong themselves or with formulated amounts of water insoluble compounds(including some polymers) to yield coatings with suitable lubricity,bonding, and solubility.

It should be understood that this disclosure is, in many respects, onlyillustrative. Changes may be made in details, particularly in matters ofshape, size, and arrangement of steps without exceeding the scope of theinvention. The scope of the invention is, of course, defined in thelanguage in which the appended claims are expressed.

While embodiments of the present invention have been shown anddescribed, various modifications may be made without departing from thescope of the present invention. The invention, therefore, should not belimited, except to the following claims, and their equivalents.Embodiments of the present invention are contemplated to have utility ina variety of blood vessels, including but not limited to coronaryarteries, carotid arteries, intracranial/cerebral arteries, inferior andsuperior vena cavae and other veins (for example, in cases of deepvenous thrombosis or pulmonary embolism), peripheral arteries, shunts,grafts, vascular defects, and chambers of the heart. This includes, butis not limited to, any vessel having a diameter of about two mm orgreater. An aspiration catheter 118 outer diameter of about seven Frenchor less is contemplated for many of the applications, though in certainapplications, it may be larger. In some embodiments, an aspirationcatheter 118 diameter of about six French or less is contemplated.Embodiments of the present invention may even be used in non-vascularapplications, for example body lumens or cavities having materialaccumulations that need to be macerated and/or removed.

It is contemplated that various combinations or subcombinations of thespecific features and aspects of the embodiments disclosed above may bemade and still fall within one or more of the inventions. Further, thedisclosure herein of any particular feature, aspect, method, property,characteristic, quality, attribute, element, or the like in connectionwith an embodiment can be used in all other embodiments set forthherein. Accordingly, it should be understood that various features andaspects of the disclosed embodiments can be combined with or substitutedfor one another in order to form varying modes of the disclosedinventions. Thus, it is intended that the scope of the presentinventions herein disclosed should not be limited by the particulardisclosed embodiments described above. Moreover, while the invention issusceptible to various modifications, and alternative forms, specificexamples thereof have been shown in the drawings and are hereindescribed in detail. It should be understood, however, that theinvention is not to be limited to the particular forms or methodsdisclosed, but to the contrary, the invention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the various embodiments described and the appended claims.Any methods disclosed herein need not be performed in the order recited.The methods disclosed herein include certain actions taken by apractitioner; however, they can also include any third-party instructionof those actions, either expressly or by implication.

The ranges disclosed herein also encompass any and all overlap,sub-ranges, and combinations thereof. Language such as “up to,” “atleast,” “greater than,” “less than,” “between,” and the like includesthe number recited. Numbers preceded by a term such as “approximately”,“about”, and “substantially” as used herein include the recited numbers(e.g., about 10%=10%), and also represent an amount close to the statedamount that still performs a desired function or achieves a desiredresult. For example, the terms “approximately”, “about”, and“substantially” may refer to an amount that is within less than 10% of,within less than 5% of, within less than 1% of, within less than 0.1%of, and within less than 0.01% of the stated amount.

What is claimed is:
 1. A system for aspirating thrombus and deliveringan agent comprising: an aspiration catheter having an aspiration lumenand a supply lumen; and at least one orifice at or adjacent a distal endof the supply lumen and in fluid communication with the aspirationlumen, the at least one orifice located proximally of the open distalend of the aspiration lumen, wherein the at least one orifice isconfigured to create a spray pattern when pressurized fluid is pumpedthrough the supply lumen such that the spray pattern is caused toimpinge on a deflection element disposed opposite the at least oneorifice when a distal end of the aspiration catheter is immersed withinan aqueous environment, and such that the spray pattern upon impingingon the deflecting elements is caused to deflect, transforming into atleast a substantially distally-oriented flow configured to exit the opendistal end of the aspiration lumen.
 2. The system of claim 1, whereinthe distally-oriented flow comprises a jet.
 3. The system of claim 1,wherein the spray pattern comprises a jet.
 4. The system of claim 1,wherein the spray pattern comprises at least two jets.
 5. The system ofclaim 1, wherein the deflection element is formed with the aspirationcatheter.
 6. The system of claim 1, wherein the deflection elements is aseparate component secure to the interior wall surface.
 7. The system ofclaim 1, wherein the deflection element comprises a ramp.
 8. The systemof claim 1, wherein the deflection element comprises a change in radiusof the interior wall surface in relation to a longitudinal axis of theaspiration lumen.
 9. The system of claim 1, wherein the deflectionelement comprises a forward ramp and a reverse ramp.
 10. The system ofclaim 1, wherein the deflection element is angled.
 11. The system ofclaim 1, wherein the deflection element is curvilinear.
 12. The systemof claim 1, wherein the deflection element comprises a concave contour.13. The system of claim 1, wherein the deflection element comprises adistally-orientate ramp.
 14. The system of claim 1, wherein thedeflection element comprises a flat surface.
 15. The system of claim 1,wherein the deflection element comprises a convex surface.
 16. Thesystem of claim 1, wherein the deflection element comprises anadjustable surface.
 17. The system of claim 17, wherein the deflectionelement comprise a balloon.
 18. The system of claim 1, wherein thedeflection element comprises a sloped surface when viewed from the side.19. The system of claim 1, wherein the deflection element is configuredto at least partially create a substantially proximally-orientedcomponent.
 20. A method for delivering an agent comprising: providing anaspiration catheter having a proximal end and a distal end andcomprising: a supply lumen having a proximal end, a distal end, and awall; an aspiration lumen having a proximal end, an open distal end, andan interior wall surface adjacent the open distal end; and at least oneorifice at or adjacent the distal end of the supply lumen, in fluidcommunication with the aspiration lumen, the at least one orificelocated proximally of the open distal end of the aspiration lumen,wherein the at least one orifice is configured to create a spray patternwhen pressurized fluid is pumped through the supply lumen such that thespray pattern is caused to impinge on a deflection element disposedopposite the at least one orifice when a distal end of the aspirationcatheter; inserting the distal end of the aspiration catheter into ablood vessel such that the open distal end of the aspiration lumen isadjacent a thrombus; and injecting an agent through the supply lumensuch that the spray pattern of the agent generally flows in a firstdirection out of the at least one orifice and against the deflectionelement within the aspiration lumen, whereby after the spray pattern ofthe agent reaches the deflection element the majority of the spraypattern of the agent flows in a second direction distally out the openend of the aspiration lumen and adjacent the thrombus, wherein thesecond direction is different from the first direction.